PubMed Health⌕ Search

Biomedical subjects

W E Müller

Publications and source records attributed to W E Müller.

At least 91 records · Page 5Linked to original sources
PubMed2000

Stimulation of protein (collagen) synthesis in sponge cells by a cardiac myotrophin-related molecule from Suberites domuncula.

The body wall of sponges (Porifera), the lowest metazoan phylum, is formed by two epithelial cell layers of exopinacocytes and endopinacocytes, both of which are associated with collagen fibrils. Here we show that a myotrophin-like polypeptide from the sponge Suberites domuncula causes the expression of collagen in cells from the same sponge in vitro. The cDNA of the sponge myotrophin was isolated; the potential open reading frame of 360 nt encodes a 120 aa long protein (Mr of 12,837). The sequence SUBDOMYOL shares high similarity with the known metazoan myotrophin sequences. The expression of SUBDOMYOL is low in single cells but high after formation of primmorph aggregates as well as in intact animals. Recombinant myotrophin was found to stimulate protein synthesis by fivefold, as analyzed by incorporation studies using [3H] lysine. In addition, it is shown that after incubation of single cells with myotrophin, the primmorphs show an unusual elongated, oval-shaped appearance. It is demonstrated that in the presence of recombinant myotrophin, the cells up-regulate the expression of the collagen gene. The cDNA for S. domuncula collagen was isolated; the deduced aa sequence shows that the collagenous internal domain is rather short, with only 24 G-x-y collagen triplets. We conclude that the sponge myotrophin causes in homologous cells the same/similar effect as the cardiac myotrophin in mammalian cells, where it is involved in initiation of cardial ventricular hypertrophy. We assume that an understanding of sponge molecular cell biology will also contribute to a further elucidation of human diseases, here of the cardiovascular system.

Amino Acid Sequence↗
PubMed2000

Cellular and biochemical responses to environmental and experimentally induced stress in sea urchin coelomocytes.

Coelomocytes are considered to be immune effectors of sea urchins. Subpopulations of coelomocytes can be purified from a total cell suspension. The proportion of each cell type can vary not only among species, but also between individuals of the same species, according to their size and physiological conditions. We tested the hypothesis that coelomocytes play a role in defense mechanisms activated by adverse external conditions. Total coelomocytes from control and stressed (temperature, pollution, and injuries) sea urchins were analyzed for their expression of the 70 kDa heat shock protein (hsp70), a well recognized stress marker. Further analysis was performed by separation of coelomocytes into subpopulations by step gradients. We demonstrated that sea urchin coelomocytes respond to temperature shock and to polluted seawater by the upregulation of hsp70. Among coelomocytes certain cells, known as red spherula cells, showed a great increase in number in animals collected from polluted seawaters or subjected to "accidental" injury. The present study confirms the immunological function of sea urchin coelomocytes, as indicated by the upregulation of the hsp70 molecular marker, and suggests that sea urchin coelomocytes can be utilized as sensitive bio-indicators of environmental stress.

Animals↗
PubMed2000

Polyphosphate in bone.

Human bone-forming osteoblasts are an excellent model to investigate the multiple functions of inorganic polyphosphates (polyP) for the following reasons: 1) they contain relatively high amounts of polyP and polyP-dependent enzymes; 2) they allow the study of both general and specific functions of these polymers, and 3) medically relevant results can be expected from these studies.

Acid Anhydride Hydrolases↗
PubMed2000

A novel binding assay for detection of 14-3-3 protein in cerebrospinal fluid from Creutzfeldt-Jakob patients.

Here we describe a simple and fast microplate assay for 14-3-3 protein, which is based on the binding of 14-3-3 protein to a chemically synthesized peptide containing the phosphorylated recognition sequence of this protein. The peptide is covalently bound to maleimide-activated microplates through reaction of the sulfhydryl group of a N-terminal cysteine residue linked to the peptide. The peptide- 14-3-.3 complexes formed are detected using--as a second recognition principle--an anti-14-3-3 protein antibody. This assay was used for measurement of 14-3-3 protein in brain (bovine) and in cerebrospinal fluid from patients with Creutzfeldt-Jakob disease (CJD) and control cases with diseases other than CJD. This novel assay allowed also the detection of low 14-3-3 protein levels present in cerebrospinal fluid, without further concentration, in contrast to conventional immunoblotting or immunoassay procedures.

14-3-3 Proteins↗
PubMed2000

Operative treatment of combined anterior and posterior cruciate ligament injuries in complex knee trauma: can the cruciate ligaments be preserved?

A retrospective study was performed focusing on operative treatment after combined anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) injuries. The operative treatment included the preservation of one or both cruciate ligaments. Twenty-eight patients, average age 30 years (range: 12-55 years), were evaluated 5.4 years (range: 1-14 years) postoperatively. Twenty-two operations were performed in patients with acute injuries (<30 days after trauma) and 6 operations in patients with chronic instabilities (>30 days after trauma). Both cruciate ligaments were preserved by suture or refixation in 16 patients. Suture of one and reconstruction of the other cruciate ligament with autologous tendon graft was performed in 12 cases. In addition, 61 procedures (meniscal suture/resection, medial/lateral reconstruction, tendon suture, and open reduction and internal fixation were performed. Postoperative treatment included continuous passive motion and protected weight bearing. Eleven (27% acute, 83% chronic) patients required revision (ACL/PCL reconstruction, osteotomy, and meniscal repair). At follow-up, 43% of the patients were very satisfied and 46% were satisfied. Seventy-one percent (89% preinjury) of the patients were able to maintain intensive and moderate International Knee Documentation Committee (IKDC) activity levels. The IKDC evaluation of the patients (acute %/chronic cases %) was graded for symptoms: A 39% (45/17), B 35% (27/67), C 15% (18/0), and D 11% (9/17); for range of motion: A 42% (36/67), B 42% (50/17), C 16% (14/17), and D 0%; and for ligaments: A 21% (18/17), B 33% (45/0), C 42% (32/83), and D 4% (5/0). Radiographic findings were A 18%, B 41%, and C 41%. Primary repair of acute injuries was superior to the delayed repair of chronic instabilities. Preservation of cruciate ligaments in acute combined ACL/PCL tears results in a satisfying knee function despite distinct residual ligament instability. Although suture of the cruciate ligaments in open technique is a therapeutic option in acute multiligamentous knee injuries, it is not recommended for the treatment of chronic instabilities.

Adult↗
PubMed1999

Origin of the interferon-inducible (2'-5')oligoadenylate synthetases: cloning of the (2'-5')oligoadenylate synthetase from the marine sponge Geodia cydonium.

In vertebrates cytokines mediate innate (natural) immunity and protect them against viral infections. The cytokine interferon causes the induction of the (2'-5')oligoadenylate synthetase [(2-5)A synthetase], whose product, (2'-5')oligoadenylate, activates the endoribonuclease L which in turn degrades (viral) RNA. Three isoforms of (2-5)A synthetases exist, form I (40-46 kDa), form II (69 kDa), and form III (100 kDa). Until now (2-5)A synthetases have only been cloned from birds and mammals. Here we describe the cloning of the first putative invertebrate (2-5)A synthetase from the marine sponge Geodia cydonium. The deduced amino acid sequence shows signatures characteristic for (2-5)A synthetases of form I. Phylogenetic analysis of the putative sponge (2-5)A synthetase indicates that it diverged first from a common ancestor of the hitherto known members of (vertebrate) (2-5)A synthetases I, (2-5)A synthetases II and III. Moreover, it is suggested that the (2-5)A synthetases II and III evolved from this common ancestor (very likely) by gene duplication. Together with earlier results on the existence of the (2'-5')oligoadenylates in G. cydonium, the data presented here demonstrate that also invertebrates, here sponges, are provided with the (2-5)A system. At present, it is assumed that this system might be involved in growth control, including control of apoptosis, and acquired its additional function in innate immune response in evolutionarily younger animals, in vertebrates.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

Evolution of the innate and adaptive immune systems: relationships between potential immune molecules in the lowest metazoan phylum (Porifera) and those in vertebrates.

Porifera (sponge) form the lowest metazoan phylum and share a common ancestor with other metazoan phyla. In the present study, it is reported that sponges possess molecules that are similar in structure to those molecules involved in the immune system in mammals. Experiments with the marine sponges Geodia cydonium and Suberites domuncula have been performed on tissue (auto- and allografting) as well as on a cellular level. The studies revealed that sponges are provided with elements of the mammalian innate immune system, such as molecules containing scavenger receptor cysteine-rich domains. Furthermore, macrophage-derived cytokine-like molecules have been identified that are up-regulated during the grafting process. In addition, the (2'-5')oligoadenylate synthetase system exists in sponges. "Precursors" of the second type of immune response in mammals, the adaptive immune system, have been traced in sponges. It is shown that the expression of a lymphocyte-derived cytokine from mammals is up-regulated during non-self-recognition in S. domuncula. Finally, in G. cydonium, two classes of receptors that comprise Ig-like domains have been identified: the receptor tyrosine kinases and the non-enzymic sponge adhesion molecules. They contain two polymorphic Ig-like domains that are grouped to the variable set of immunoglobulins. The expression of these molecules is also up-regulated during the grafting process. It is concluded that sponges are already provided with a series of elements used in higher vertebrates for both the innate and the adaptive immune recognition.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

Ethylene modulates gene expression in cells of the marine sponge Suberites domuncula and reduces the degree of apoptosis.

Sponges (phylum Porifera) live in an aqueous milieu that contains dissolved organic carbon. This is degraded photochemically by ultraviolet radiation to alkenes, particularly to ethylene. This study demonstrates that sponge cells (here the demosponge Suberites domuncula has been used), which have assembled to primmorphs, react to 5 microM ethylene with a significant up-regulation of intracellular Ca(2+) concentration and with a reduction of starvation-induced apoptosis. In primmorphs from S. domuncula the expression of two genes is up-regulated after exposure to ethylene. The cDNA of the first gene (SDERR) isolated from S. domuncula encodes a potential ethylene-responsive protein, termed ERR_SUBDO; its putative M(r) is 32,704. Data bank search revealed that the sponge polypeptide shares high similarity (82% on amino acid level) with the corresponding plant molecule, the ethylene-inducible protein from Hevea brasiliensis. Until now no other metazoan ethylene-responsive proteins have been identified. The second gene, whose expression is up-regulated in response to ethylene is a Ca(2+)/calmodulin-dependent protein kinase II. Its cDNA, SDCCdPK, encodes a M(r) 54,863 putative kinase that shares 69% similarity with the corresponding enzyme from Drosophila melanogaster. The expression of both genes in primmorphs from S. domuncula is increased by approximately 5-fold after a 3-day incubation period with ethylene. It is concluded that also metazoan cells, with sponge cells as a model, may react to ethylene with an activation of cell metabolism including gene induction.

Amino Acid Sequence↗
PubMed1999

Gene structure and function of tyrosine kinases in the marine sponge Geodia cydonium: autapomorphic characters in Metazoa.

Porifera (sponges) represent the most ancient, extant metazoan phylum. They existed already prior to the 'Cambrian Explosion'. Based on the analysis of aa sequences of informative proteins, it is highly likely that all metazoan phyla evolved from only one common ancestor (monophyletic origin). As 'autapomorphic' proteins which are restricted to Metazoa only, integrin receptors, receptors with scavenger receptor cysteine-rich repeats, neuronal-like receptors and protein-tyrosine kinases (PTKs) have been identified in Porifera. From the marine sponge Geodia cydonium, a receptor tyrosine kinase (RTK) has been cloned that comprises the characteristic structural topology known from other metazoan RTKs; an extracellular domain, the transmembrane region, the juxtamembrane region and the TK domain. Only two introns, within the coding region of the RTK gene, could be found, which separate the two highly polymorphic immunoglobulin-like domains, found in the extracellular region of the enzyme. The functional role of this sponge RTK could be demonstrated both in situ (grafting experiments) and in vitro (increase of intracellular Ca2+ level). Upstream of this RTK gene, two further genes coding for tyrosine kinases (TK) have been identified. Both are intron-free. The deduced aa sequence of the first gene shows no transmembrane segment; from the second gene--so far--only half of its catalytic domain is known. A phylogenetic analysis with the TK domains from these sequences and a fourth, from a novel scavenger RTK (all domains comprise the signature for the TK class II receptors), showed that they are distantly related to the insulin and insulin-like receptors. The presented findings support the 'introns-late' hypothesis for such genes that encode 'metazoan' proteins. It is proposed that the TKs evolved from protein-serine/threonine kinases through modularization and subsequent exon shuffling. After formation of the ancestral TKs, the modules lost the framing introns to protect the evolutionary novelty. Since cell culture systems of sponges are now available, it can be expected that soon also those mechanisms that control the developmental programs will be unravelled.

Amino Acid Sequence↗
PubMed1999

A microplate assay for DNA damage determination (fast micromethod).

A rapid and convenient procedure for DNA damage determination in cell suspensions and solid tissues on single microplates was developed. The procedure is based on the ability of commercially available fluorochromes to interact preferentially with dsDNA in the presence of ssDNA, RNA, and proteins at high pH (>12.0), thus allowing direct measurements of DNA denaturation without sample handling or stepwise DNA separations. The method includes a simple and rapid 40-min sample lysis in the presence of EDTA, SDS, and high urea concentration at pH 10, followed by time-dependent DNA denaturation at pH 12.4 after NaOH addition. The time course and the extent of DNA denaturation is followed in a microplate fluorescence reader at room temperature for less than 1 h. The method requires only 30 ng DNA per single well and could conveniently be used whenever fast analysis of DNA integrity in small samples has to be done, e.g., in patients' lymphocytes after irradiation or chemotherapy (about 3000 cells per sample), in solid tissues or biopsies after homogenization (about 25 microg tissue per well), or in environmental samples for genotoxicity assessment.

Animals↗
PubMed1999

Promoter and exon-intron structure of the protein kinase C gene from the marine sponge Geodia cydonium: evolutionary considerations and promoter activity.

We report the gene structure of a key signaling molecule from a marine sponge, Geodia cydonium. The selected gene, which codes for a classical protein kinase C (cPKC), comprises 13 exons and 12 introns; the introns are, in contrast to those found in cPKC from higher Metazoa, small in size ranging from 93 nt to 359 nt. The complete gene has a length of 4229 nt and contains exons which encode the characteristic putative regulatory and catalytic domains of metazoan cPKCs. While in the regulatory domain only one intron is in phase 0, in the catalytic domain most introns are phase 0 introns, suggesting that the latter only rarely undergo module duplication. The 5'-flanking sequence of the sponge cPKC gene contains a TATA-box like motif which is located 35-26 nt upstream from the start of the longest sequenced cDNA. This 5'-flanking sequence was analyzed for promoter activity. The longest fragment (538 nt) was able to drive the expression of luciferase in transient transfections of NIH 3T3 fibroblasts; the strong activity of the sponge promoter was found to be half the one displayed by the SV40 reference promoter. Deletion analysis demonstrates that the AP4 site and the GC box which is most adjacent to the TATA box are the crucial elements for maximal promoter activity. The activity of the promoter is not changed in 3T3 cells which are kept serum starved or in the presence of a phorbol ester. In conclusion, these data present the phylogenetically oldest cPKC gene which contains in the 5'-flanking region a promoter functional in the heterologous mammalian cell system.

3T3 Cells↗
PubMed1999

Towards an understanding of the molecular basis of immune responses in sponges: the marine demosponge Geodia cydonium as a model.

The phylogenetic position of the phylum Porifera (sponges) is near the base of the kingdom Metazoa. During the last few years, not only rRNA sequences but, more importantly, cDNA/genes that code for proteins have been isolated and characterized from sponges, in particular from the marine demosponge Geodia cydonium. The analysis of the deduced amino acid sequences of these proteins allowed a molecular biological approach to the question of the monophyly of the Metazoa. Molecules of the extracellular matrix/basal lamina, with the integrin receptor, fibronectin, and galectin as prominent examples, and of cell-surface receptors (tyrosine kinase receptor), elements of sensory systems (crystallin, metabotropic glutamate receptor) as well as homologs/modules of an immune system (immunoglobulin-like molecules, scavenger receptor cysteine-rich [SRCR]- and short consensus repeats [SCR]-repeats), classify the Porifera as true Metazoa. As living fossils, provided with simple, primordial molecules allowing cell-cell and cell-matrix adhesion as well as processes of signal transduction as known in a more complex manner from higher Metazoa, sponges also show pecularities not known in later phyla. In this paper, the adhesion molecules presumably involved in the sponge immune system are reviewed; these are the basic adhesion molecules (galectin, integrin, fibronectin, and collagen) and especially the highly polymorphic adhesion molecules, the receptor tyrosine kinase as well as the polypeptides comprising scavenger receptor cysteine-rich (SRCR) and short consensus repeats (SCR) modules. In addition, it is reported that in the model sponge system of G. cydonium, allogeneic rejection involves an upregulation of phenylalanine hydroxylase, an enzyme initiating the pathway to melanin synthesis.

Amino Acid Sequence↗
PubMed1999

Evolutionary relationships of Metazoa within the eukaryotes based on molecular data from Porifera.

Recent molecular data provide strong support for the view that all metazoan phyla, including Porifera, are of monophyletic origin. The relationship of Metazoa, including the Porifera, to Plantae, Fungi and unicellular eukaryotes has only rarely been studied by using cDNAs coding for proteins. Sequence data from rDNA suggested a relationship of Porifera to unicellular eukaryotes (choanoflagellates). However, ultrastructural studies of choanocytes did not support these findings. In the present study, we compared amino acid sequences that are found in a variety of metazoans (including sponges) with those of Plantae, Fungi and unicellular eukaryotes, to obtain an answer to this question. We used the four sequences from 70 kDa heat-shock proteins, the serine-threonine kinase domain found in protein kinases, beta-tubulin and calmodulin. The latter two sequences were deduced from cDNAs, isolated from the sponge Geodia cydonium for the phylogenetic analyses presented. These revealed that the sponge molecules were grouped into the same branch as the Metazoa, which is statistically (significantly) separated from those branches that comprise the sequences from Fungi, Plantae and unicellular eukaryotes. From our molecular data it seems evident that the unicellular eukaryotes existed at an earlier stage of evolution, and the Plantae and especially the Fungi and the Metazoa only appeared later.

Amino Acid Sequence↗
PubMed1999

Induction of DNA strand breaks and expression of HSP70 and GRP78 homolog by cadmium in the marine sponge Suberites domuncula.

The marine sponge Suberites domuncula was used as a bioindicator to study the effects of cadmium on the occurrence of DNA strand breakage and on the induction of the expression of the stress biomarkers, heat shock protein 70 (HSP70) and glucose-regulated protein 78 (GRP78) homolog. The cDNA encoding GRP78 homolog from S. domuncula was isolated and characterized. The GRP78 cDNA has a length of 2.1 kb and displays characteristic features of the HSP70 family; it encodes an aa sequence of Mr 72,000. Exposure of S. domuncula to 1 mg/L of cadmium chloride for 24 h caused a strong (16. 6-fold) increase in cadmium content to 7.7 microg/g wet weight of sponge tissue; after an incubation period of 6 days, the accumulation was 20.4-fold. The increase in cadmium content was paralleled by a transient decrease in zinc content at days 1 and 3. Exposure of S. domuncula to cadmium chloride also resulted in a marked increase in the number of DNA single strand breaks, as assessed by a recently developed fast and sensitive microplate assay. The maximum increase in DNA damage was observed after an incubation of 12 h in the presence of 1 mg/L of cadmium chloride; after longer incubation, the number of damaged sites decreased, most likely due to DNA repair. Quantitative analysis of the expression of HSP70 (Mr 73 kDa) revealed that onset of maximal levels of HSP70 depends on the concentration of cadmium chloride in the ambient seawater. Maximal induction (8.9-fold increase compared to control) of HSP70 following exposure to 1 mg/L of cadmium chloride was found after 12 h, while longer incubation periods (3-6 days) were needed to reach maximum levels of HSP70 in the presence of lower concentrations of cadmium chloride (0.1 mg/L and 0.01 mg/L). Northern blot analysis revealed that the level of the 2.0 kb sponge GRP78 homolog mRNA transiently increased under cadmium stress; the maximum increase in the presence of 0.1 mg/L of cadmium chloride was observed at day 3. Our results suggest that sponges are useful indicator organisms to assess the genotoxic risks of cadmium pollution in marine environments.

Amino Acid Sequence↗
PubMed1999

Induction of hsp70 by the herbicide oxyfluorfen (Goal) in the Egyptian Nile fish, Oreochromis niloticus.

This paper deals with the expression of the biomarker hsp70 in the liver and kidney of the freshwater fish Oreochromis niloticus following exposure to the herbicide oxyfluorfen (Goal). Fishes were exposed to three concentrations, the 96-h LC50 (3 mg/L), the 96-h (1/2)LC50 (1.5 mg/L), and the 96-h (1/4)LC50 (0.75 mg/L) of oxyfluorfen for 6, 15, and 24 days, respectively, and samples were taken at three different time periods for each concentration. The livers responded to the herbicide by an induction of the expression of both the constitutive (hsp75; Mr 75 kDa) and the inducible (hsp73; Mr 73 kDa) hsp70 proteins. In kidney, the herbicide induced a time-dependent increase in the expression of the constitutive hsp70 (hsp75) as well, but the inducible hsp70 (hsp73) required much longer incubation periods to reach maximal levels (15 and 24 days). Our results suggest that expression of hsp70 in fish is a sensitive indicator of cellular responses to herbicide exposure in the aquatic environment.

Animals↗
PubMed1999

Cloning and expression of new receptors belonging to the immunoglobulin superfamily from the marine sponge Geodia cydonium.

A cDNA encoding a receptor tyrosine kinase (RTK) was previously cloned and expressed from the marine sponge (Porifera) Geodia cydonium. In addition to the two intracellular regions characteristic for RTKs, two immunoglobulin (Ig)-like domains are found in the extracellular part of the sponge RTK. In the present study it is shown that no further Ig-like domain is present in the upstream region of the cDNA as well as of the gene hitherto known from the sponge RTK. Two different full-length cDNAs have been isolated and characterized in the present study, which possess two Ig-like domains, one transmembrane segment, and only a short intracellular part, without a TK domain. The two deduced polypeptides were preliminarily termed sponge adhesion molecules (SAM). The longer form of the SAM, GCSAML, encodes a deduced aa sequence, GCSAML, which comprises in the open reading frame 505 amino acids (aa) and has a calculated Mr of 53911. The short form, GCSAMS, has 313 aa residues and an Mr of 33987. The two Ig-like domains in GCSAML and GCSAMS are highly similar to the corresponding Ig-like domains in the RTKs from G. cydonium; the substitutions on both the aa and nt level are restricted to a few sites. Phylogenetic analyses revealed that the Ig-like domain 1 is similar to the human Ig lambda chain variable region, while the Ig-like domain 2 is related more closely to the human Ig heavy chain variable region. Transplantation experiments (autografting) were performed to demonstrate that the level of expression of the two new genes, GCSAML and GCSAMS, is upregulated during the self/self fusion process. Immunohistochemical analyses using antibodies raised against the two Ig-like domains demonstrate a strong expression in the fusion zone between graft and host. This finding has been supported by northern blotting experiments that revealed that especially GCSAML is strongly upregulated after autografting (up to 12-fold); the expression of GCSAMS reaches a value of 5-fold if compared with the controls. The results presented here demonstrate that the expression of the new molecules described, comprising two Ig-like domains, is upregulated during the process of autograft fusion.

Amino Acid Sequence↗
PubMed1999

Origin of neuronal-like receptors in Metazoa: cloning of a metabotropic glutamate/GABA-like receptor from the marine sponge Geodia cydonium.

To date, no conclusive evidence has been presented for the existence of neuronal-like elements in Porifera (sponges). In the present study, isolated cells from the marine sponge Geodia cydonium are shown to react to the excitatory amino acid glutamate with an increase in the concentration of intracellular calcium [Ca2+]i. This effect can also be observed when the compounds L-quisqualic acid (L-QA) or L-(+)-2-amino-4-phosphonobutyric acid (L-AP-4) are used. The effect of L-QA and L-AP-4, both agonists for metabotropic glutamate receptors (mGluRs), can be abolished by the antagonist of group I mGluRs, (RS)-alpha-methyl-4-carboxyphenylglycine. These data suggest that sponge cells contain an mGluR-like protein. A cDNA encoding rat mGluR subtype 1 has been used to identify the complete nucleotide sequence of G. cydonium cDNA coding for a 528-amino-acid-long protein (59 kDa) that displays marked overall similarity to mGluRs and to gamma-aminobutyric acid B receptors. The deduced sponge polypeptide, termed putative mGlu/GABA-like receptor, displays the highest similarity to the two families of metabotropic receptors within the transmembrane segment. The N-terminal part of the sponge sequence shows similarity to mGluR4 and mGluR5. These findings suggest that the earliest evolutionary metazoan phylum, the Porifera, possesses a sophisticated intercellular communication and signaling system, as seen in the neuronal network of higher Metazoa.

Amino Acid Sequence↗