Biomedical subjects

Kausik Si

Publications and source records attributed to Kausik Si.

7 recordsLinked to original sources

PubMed2006

RISC-y Memories.

Local protein synthesis in the synapse is required for synaptic plasticity and has been implicated in learning and memory. However, direct evidence that behavioral training induces local protein synthesis has been lacking. In this issue of Cell, Ashraf et al. (2006) observe persistent local protein synthesis in the antennal lobe synapses of the fruit fly following olfactory-avoidance learning. This protein synthesis is regulated by the RNA-induced silencing complex (RISC).

Animals↗

PubMed2004

The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth.

Recent cellular and molecular studies of both implicit and explicit memory storage suggest that experience-dependent modulation of synaptic strength and structure is a fundamental mechanism by which these diverse forms of memory are encoded and stored. For both forms of memory storage, some type of synaptic growth is thought to represent the stable cellular change that maintains the long-term process. In this review, we discuss recent findings on the molecular events that underlie learning-related synaptic growth in Aplysia and discuss the possibility that an active, prion-based mechanism is important for the maintenance of the structural change and for the persistence of long-term memory.

Animals↗

PubMed2003

A neuronal isoform of the aplysia CPEB has prion-like properties.

Prion proteins have the unusual capacity to fold into two functionally distinct conformations, one of which is self-perpetuating. When yeast prion proteins switch state, they produce heritable phenotypes. We report prion-like properties in a neuronal member of the CPEB family (cytoplasmic polyadenylation element binding protein), which regulates mRNA translation. Compared to other CPEB family members, the neuronal protein has an N-terminal extension that shares characteristics of yeast prion-determinants: a high glutamine content and predicted conformational flexibility. When fused to a reporter protein in yeast, this region confers upon it the epigenetic changes in state that characterize yeast prions. Full-length CPEB undergoes similar changes, but surprisingly it is the dominant, self-perpetuating prion-like form that has the greatest capacity to stimulate translation of CPEB-regulated mRNA. We hypothesize that conversion of CPEB to a prion-like state in stimulated synapses helps to maintain long-term synaptic changes associated with memory storage.

Animals↗

PubMed2003

A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia.

Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark.

Actins↗

PubMed2003

Axonal transport of eukaryotic translation elongation factor 1alpha mRNA couples transcription in the nucleus to long-term facilitation at the synapse.

Long-term synaptic plasticity requires both gene expression in the nucleus and local protein synthesis at synapses. The effector proteins that link molecular events in the cell body with local maintenance of synaptic strength are not known. We now show that treatment with serotonin (5-HT) that produces long-term facilitation induces the Aplysia eukaryotic translation elongation factor 1alpha (Ap-eEF1A) as a late gene that might serve this coupling function in sensory neurons. Although the translation factor is induced, it is not transported into axon processes when the stimulation with 5-HT was restricted to the cell body. In contrast, its mRNA is transported when 5-HT was applied to both cell body and synapses. Intracellular injection of antisense oligonucleotides or antibodies that block the induction and expression of Ap-eEF1A do not affect the initial expression of long-term facilitation but do block its maintenance beyond 24 h. The transport of eEF1A protein and its mRNA to nerve terminals suggests that the translation factor plays a role in the local protein synthesis that is essential for maintaining newly formed synapses.

Animals↗

PubMed2003

Two previously undescribed members of the mouse CPEB family of genes and their inducible expression in the principal cell layers of the hippocampus.

Cytoplasmic polyadenylation element-binding (CPEB) proteins control polyadenylation-induced translation in early development. Studies in oocytes led to the delineation of Xenopus CPEB, the first member of the family to be identified, and its mouse homologue mCPEB-1. Recently, a second mouse family member, mCPEB-2, has been described in germ cells. Increasing evidence also implicates CPEB proteins as being important in the hippocampus, where these proteins are thought to regulate local protein synthesis and synaptic plasticity. We therefore carried out a systematic screen for CPEB genes in the mouse brain and report two previously undescribed gene family members: mCPEB-3 and -4. We next examined the expression of all four genes in the hippocampus and found that mCPEB-1, -2, and -4 transcripts are expressed in the principal cell layer in the CA3 and CA1 region and in the dentate gyrus of the hippocampus. mCPEB-3 was barely expressed in naïve animals but together with mCPEB-4 was strongly up-regulated after injection of kainate to initiate seizure activity. Whereas mCPEB-1 is regulated by the Aurora kinase, mCPEB-2, -3, and -4 do not contain Aurora kinase phosphorylation sites. However, alternative splice isoforms of mCPEB-2, -3, and -4 encode the so-called B region with phosphorylation sites for cAMP-dependent protein kinase, calcium/calmodulin-dependent protein kinase II, and S6 kinase. Only isoforms that encode the B region were expressed in the principal cell layer. Coexpression of mCPEB-1 and the B region-containing splice isoforms suggests that a variety of different signaling pathways can recruit CPEB activity in hippocampal neurons.

Amino Acid Sequence↗

PubMed2003

Phosphorylation of mammalian eukaryotic translation initiation factor 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that phosphorylation of Tif6p regulates its nucleocytoplasmic distribution and is required for yeast cell growth.

The synthesis of 60S ribosomal subunits in Saccharomyces cerevisiae requires Tif6p, the yeast homologue of mammalian eukaryotic translation initiation factor 6 (eIF6). In the present work, we have isolated a protein kinase from rabbit reticulocyte lysates on the basis of its ability to phosphorylate recombinant human eIF6. Mass spectrometric analysis as well as antigenic properties of the purified kinase identified it as casein kinase I. The site of in vitro phosphorylation, which is highly conserved from yeast to mammals, was identified as the serine residues at positions 174 (major site) and 175 (minor site). The homologous yeast protein Tif6p was also phosphorylated in vivo in yeast cells. Mutation of Tif6p at serine-174 to alanine reduced phosphorylation drastically and caused loss of cell growth and viability. When both Ser-174 and Ser-175 were mutated to alanine, phosphorylation of Tif6p was completely abolished. Furthermore, while wild-type Tif6p was distributed both in nuclei and the cytoplasm of yeast cells, the mutant Tif6p (with Ser174Ala and Ser175Ala) became a constitutively nuclear protein. These results suggest that phosphorylatable Ser-174 and Ser-175 play a critical role in the nuclear export of Tif6p.

Active Transport, Cell Nucleus↗