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H Van Heerikhuizen

Publications and source records attributed to H Van Heerikhuizen.

8 recordsLinked to original sources
PubMed1998

Towards understanding the role of insulin in the brain: lessons from insulin-related signaling systems in the invertebrate brain.

Insulin is a molecule that has played a key role in several of the most important landmarks in medical and biological research. It is one of the most extensively studied protein hormones, and its structure and function have been elucidated in many vertebrate species, ranging from man to hagfish and turkey. The structure, function as well as tissue of synthesis of vertebrate insulins are strictly conserved. The structural identification of insulin-related peptides from invertebrates has disrupted the picture of an evolutionary stable peptide hormone. Insulin-related peptides in molluscs and insects turned out to be a structurally diverse group encoded by large multi-gene families that are uniquely expressed in the brain and serve functions different from vertebrate insulin. In this review, we discuss invertebrate insulins in detail. We examine how these peptides relate to the model role that vertebrate insulin has played over the years; however, more importantly, we discuss several unique principles that can be learned from them. We show how diversity of these peptides is generated at the genetic level and how the structural diversity of the peptides is linked to the exclusive presence of a single type of neuronal insulin receptor-related receptor. We also discuss the fact that the invertebrate peptides, in addition to a hormonal role, may also act in a synaptic and/or nonsynaptic fashion as transmitters/neuromodulators on neurons in the brain. It can be expected that the use of well-defined neuronal preparations in invertebrates may lead to a further understanding of these novel functions and may act as guide preparations for a possible role of insulin and its relatives in the vertebrate brain.

Amino Acid Sequence↗
PubMed1998

Regulation of expression of the amino acid transporter gene BAP3 in Saccharomyces cerevisiae.

The BAP3 gene of Saccharomyces cerevisiae encodes a protein with a high similarity to the BAP2 gene product, a high-affinity permease for branched-chain amino acids. In this paper, we show that, like BAP2, the expression of the BAP3 gene in S. cerevisiae is induced by the addition of branched-chain amino acids to the medium. Unexpectedly, most other naturally occurring L-amino acids found in proteins (with the exception of proline, lysine, arginine and histidine) have the same effect on the expression of BAP3. The induction of BAP3 expression appears to be dependent on Stp1p, a nuclear protein, previously shown to be involved in pre-tRNA maturation and also required for the expression of BAP2, as induction is no longer observed in an stp1 - mutant. The transcriptional regulator Leu3p is not involved in the induction of BAP3 expression, but may act as a repressor of BAP3 expression in the absence of leucine, as can be inferred from a transcriptional analysis in a Deltaleu3 mutant. By extensive deletion analysis of the BAP3 promoter fused to a GUS reporter, as well as by fusions of different parts of the BAP3 promoter to a LacZ reporter, we have found that a portion of the BAP3 promoter from - 418 to - 392 relative to the ATG start codon is both necessary and sufficient for the Stp1p-dependent induction of BAP3 expression by (most) amino acids. We have therefore named this sequence UASaa (amino acid-dependent upstream activator sequence). Neither Stp1p nor Leu3p appear to bind to the UASaa, at least in vitro, as judged from gel retardation assays. Sequences similar to the UASaa can be found in the promoters of BAP2, PTR2 and TAT1; genes that, like BAP3, encode permeases inducible by amino acids, suggesting that amino acid induction of all these genes is exerted via a common mechanism.

Amino Acid Transport Systems↗
PubMed1997

Molecular cloning and pharmacological characterization of a molluscan octopamine receptor.

We describe the cloning and functional expression of a cDNA encoding a novel G protein-coupled receptor, which was isolated from the central nervous system of the pond snail Lymnaea stagnalis. The amino acid sequence predicted by this cDNA shows highest similarity with the sequence of the Locusta tyramine receptor, the Drosophila tyramine/octopamine receptor, and the mammalian alpha-adrenergic receptors. On expression in mammalian cells, [3H]rauwolscine, an alpha2-adrenergic receptor antagonist, binds with high affinity (K(D) = 2.9 x 10(-9) M) to the receptor. Of several tested neurotransmitters, octopamine (which is considered to be the invertebrate counterpart of norepinephrine) showed the highest affinity (1.9 x 10(-6) M) for the receptor. Therefore, we consider this receptor to be the first true octopamine receptor to be cloned. The ligand binding properties of the novel receptor, designated Lym oa1, seem to be distinct from any of the binding profiles described for octopamine receptors in tissue preparations. Although the pharmacological profile of Lym oa1 shows some similarity with that of Tyr/Oct-Dro and Tyr-Loc, there are also clear differences. In particular, phentolamine, chlorpromazine, and mianserine display markedly higher affinities for Lym oa1 than for the insect receptors. As far as the vertebrate adrenergic receptors are concerned, the ligand binding properties of Lym oa1 resemble alpha2-adrenergic receptors more than they do alpha- or beta-adrenergic receptors. Octopaminergic stimulation of Lym oa1 induces an increase in both inositol phosphates and cAMP (EC50 = 9.1 x 10(-7) M and 5.1 x 10(-6) M, respectively). This is in contrast to the signal transduction pathways described for the related tyramine- and alpha2-adrenergic receptors, which couple in an inhibitory way to adenylyl cyclase.

Amino Acid Sequence↗
PubMed1996

Functional characterisation of a 5-HT2 receptor cDNA cloned from Lymnaea stagnalis.

A G-protein-coupled receptor (5-HT2Lym) resembling members of the 5-HT2 receptor subfamily was cloned from the mollusc Lymnaea stagnalis. Serotonin induces a concentration-dependent increase in intracellular inositol phospates in HEK293 cells expressing this receptor (EC50 = 114 nM). 5-HT2Lym differs from mammalian 5-HT2 receptors by the presence of a large amino-terminal region. This large domain appears to preclude an adequate level of expression of 5-HT2Lym in HEK293. Therefore, we constructed a cDNA encoding an amino-terminally truncated receptor (delta N-5-HT2Lym) that appeared to be much better expressed in HEK293 cells. delta N-5-HT2Lym-expressing cells exhibit a serotonin-induced stimulation of phosphatidylinositol bisphosphate hydrolysis (EC50 = 11.4 nM) and a high-affinity binding of the 5-HT2-selective antagonist [3H]mesulergine (Kd = 4 nM). Inhibition of this binding by several 5-HT2 antagonists and agonists revealed a pharmacological profile most closely resembling those of 5HT2Dro, 5-HT2B and 5-HT2C.

Amino Acid Sequence↗
PubMed1993

Alternative splicing generates diversity of VD1/RPD2 alpha peptides in the central nervous system of Lymnaea stagnalis.

1. Two giant peptidergic neurons, VD1 and RPD2, of the visceral ganglion and right parietal ganglion of Lymnaea stagnalis, respectively, play an important role in the modulation of complex physiological and behavioral adjustments that occur as a result of changes in O2 availability. 2. By cDNA cloning, we have identified two types of VD1/RPD2 transcripts expressed in VD1 and RPD2. In addition, these transcripts are also expressed in other neurons. 3. Both transcripts encode distinct yet related VD1/RPD2 preprohormones that may be cleaved to yield distinct but overlapping sets of neuropeptides. 4. Using the polymerase chain reaction technique, we could show the existence of additional splice variants. 5. Analysis of the organization of the VD1/RPD2 gene indicates that the alpha peptide coding region is interrupted by a number of introns. 6. We concluded that the mRNA segment encoding the alpha peptide domain of the VD1/RPD2 preprohormones is alternatively spliced, thus generating different alpha peptides.

Amino Acid Sequence↗
PubMed1991

Characterization and evolutionary aspects of a transcript encoding a neuropeptide precursor of Lymnaea neurons, VD1 and RPD2.

We isolated and characterized a cDNA clone encoding the major prohormone of VD1 and RPD2, two electrotonically coupled identified neurons in the central nervous system of the freshwater snail, Lymnaea stagnalis. The VD1/RPD2 prohormone may be cleaved to generate a set of 4 different neuropeptides, called epsilon, delta, alpha 1 and beta peptides, as well as a single aspartate. Since VD1 and RPD2 probably are involved in O2 perception and modulation of cardio-respiratory functions, it is thought that the neuropeptides synthesized and released by these neurons coordinate the adaptive physiological and behavioural processes that occur in response to changes in O2 availability. Comparison of the Lymnaea VD1/RPD2 precursor with two related precursors, prohormones R15-1 and R15-2, identified from neuron R15 in the marine mollusc Aplysia californica revealed a similar pattern of organization of the preprohormones. The overall homology is rather low, however, detailed comparisons show a highly differential pattern of conservation of peptide regions on the precursors.

Amino Acid Sequence↗
PubMed1988

Isolation, characterization, and evolutionary aspects of a cDNA clone encoding multiple neuropeptides involved in the stereotyped egg-laying behavior of the freshwater snail Lymnaea stagnalis.

The cerebral neurosecretory caudodorsal cells (CDCs) of the freshwater pulmonate snail Lymnaea stagnalis control egg laying, an event that involves a pattern of stereotyped behaviors. The CDCs synthesize and release multiple peptides, among which is the ovulation hormone (CDCH). It is thought that each peptide controls a specific aspect of the processes involved in egg laying. We isolated and characterized a CDC-specific cDNA clone that encodes the ovulation hormone (CDCH). RNA blot analysis and in situ hybridization experiments demonstrated that the CDCs are the major cell groups in the cerebral ganglia that transcribe the CDCH gene. In addition to CDCH, the 259-amino acid-long CDCH preprohormone contains 11 other predicted peptides. The overall homology of the CDCH preprohormone with the egg-laying hormone (ELH) preprohormones of the marine opisthobranch snails Aplysia californica and A. parvula is very low (29 and 26%, respectively). However, a more detailed comparison revealed a highly differential pattern of conservation of peptide regions. Significant homology was found between the regions containing (1) CDCH and ELH, (2) repeated pentapeptides, (3) alpha-caudodorsal cell peptide and alpha-bag cell peptide, and (4) 2 regions representing as yet unidentified peptides. Insignificant homology was found when comparing regions containing the other predicted peptides. The conserved peptides probably control similar aspects of the egg-laying fixed action patterns in these distantly related gastropod species. The pentapeptide region exhibits the highest level of homology (75%); in addition, an extra pentapeptide has been generated on the CDCH precursor. This indicates a vital function of these peptides in Aplysia, as well as in Lymnaea species.

Amino Acid Sequence↗