Kelsey C Martin
Professor, Biological Chemistry, University of California Los Angeles
Professor, Psychiatry and Biobehavioral Sciences, University of California Los Angeles
UCLA Biol Chem
615 Charles E Young
BOX 951737, 390-B BSRB
Los Angeles, CA 90095
615 Charles E. Young Dr. S.
Los Angeles, CA 90095
How Does the Brain Store Memories?
Experience changes the strength and number of synaptic connections between neurons in the brain. This process, known as synaptic plasticity, provides a cellular mechanism for memory storage. Research in the Martin lab is aimed at understanding the cell and molecular biology of synaptic plasticity in mouse and Aplysia model systems. The results of their research shed light not only on healthy brain function, but also on the causes of many brain disorders in which neuronal plasticity and memory formation are altered, including mental retardation, autism spectrum disorders, drug addiction, anxiety disorders, and Alzheimer’s disease.
Long-term forms of plasticity, such as those underlying long-term memory, require new RNA and protein synthesis. This means that signals are transported from the synapse, where they are generated, to the nucleus, where they alter transcription. The transport of molecules from the synapse to the nucleus of neurons is particularly challenging because synapses are often very far from the cell body. The Martin lab has discovered a role for the active transport of signals from stimulated synapses to the nucleus during long-term neuronal plasticity. Current research is aimed at identifying synaptically localized signaling molecules that undergo stimulus-induced active nuclear import during plasticity, and at understanding the cell biological pathways that mediate long-distance retrograde transport from synapse to nucleus. In studies focused on the transcriptional regulator CRTC1, the Martin lab is exploring how specific patterns of neuronal stimulation trigger specific programs of transcription, and how neuromodulators such as dopamine and norepinephrine regulate the programs of gene expression that give rise to long-lasting plasticity. This work provides molecular insights into the role of emotion and attention in memory formation.
Research in the Martin lab also addresses the mechanisms by which transcription-dependent plasticity can occur at subsets of the thousands of synapses that are made by an individual neuron. Dr. Martin and her colleagues have shown that one important mechanism for restricting gene expression to stimulated synapses involves the regulated translation of synaptically localized mRNAs. Studies in her lab are aimed at identifying the populations of mRNAs that localize to synapses, the molecular mechanisms underlying the localization and translation of these mRNAs, as well as the function of local translation in long-term memory. Recent transcriptome and translatome profiling experiments suggest that the regulation of gene expression in neurons is highly decentralized and compartmentalized during plasticity, with transcriptional regulation placing the entire neuronal arbor in a state of readiness to respond to local cues via local translation to change the structure and function of subsets of synapses.
- Herbst WA, Deng W, Wohlschlegel JA, Achiro JM, Martin KC. Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription.. The Journal of cell biology, 2021.
- Martin KC, Czernin J. A Conversation Between Kelsey Martin and Johannes Czernin.. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2020.
- Holt CE, Martin KC, Schuman EM. Local translation in neurons: visualization and function.. Nature structural & molecular biology, 2019.
- Merkurjev D, Hong WT, Iida K, Oomoto I, Goldie BJ, Yamaguti H, Ohara T, Kawaguchi SY, Hirano T, Martin KC, Pellegrini M, Wang DO. Author Correction: Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts.. Nature neuroscience, 2018.
- Merkurjev D, Hong WT, Iida K, Oomoto I, Goldie BJ, Yamaguti H, Ohara T, Kawaguchi SY, Hirano T, Martin KC, Pellegrini M, Wang DO. Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts.. Nature neuroscience, 2018.
- Octeau JC, Chai H, Jiang R, Bonanno SL, Martin KC, Khakh BS. An Optical Neuron-Astrocyte Proximity Assay at Synaptic Distance Scales.. Neuron, 2018.
- Vuong CK, Wei W, Lee JA, Lin CH, Damianov A, de la Torre-Ubieta L, Halabi R, Otis KO, Martin KC, O'Dell TJ, Black DL. Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1.. Neuron, 2018.
- Van Driesche SJ, Martin KC. New frontiers in RNA transport and local translation in neurons.. Developmental neurobiology, 2018.
- Fontes MM, Guvenek A, Kawaguchi R, Zheng D, Huang A, Ho VM, Chen PB, Liu X, O'Dell TJ, Coppola G, Tian B, Martin KC. Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.. Scientific reports, 2017.
- Gao J, Marosi M, Choi J, Achiro JM, Kim S, Li S, Otis K, Martin KC, Portera-Cailliau C, Tontonoz P. The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.. eLife, 2017.
- Herbst WA, Martin KC. Regulated transport of signaling proteins from synapse to nucleus.. Current opinion in neurobiology, 2017.
- Chen PB, Kawaguchi R, Blum C, Achiro JM, Coppola G, O'Dell TJ, Martin KC. Mapping Gene Expression in Excitatory Neurons during Hippocampal Late-Phase Long-Term Potentiation.. Frontiers in molecular neuroscience, 2017.
- Martin KC. Tips for Young Scientists on the Junior Faculty/Independent Investigator Job Search.. Neuron, 2017.
- Poo MM, Pignatelli M, Ryan TJ, Tonegawa S, Bonhoeffer T, Martin KC, Rudenko A, Tsai LH, Tsien RW, Fishell G, Mullins C, Gonçalves JT, Shtrahman M, Johnston ST, Gage FH, Dan Y, Long J, Buzsáki G, Stevens C. What is memory? The present state of the engram.. BMC biology, 2016.
- Damianov A, Ying Y, Lin CH, Lee JA, Tran D, Vashisht AA, Bahrami-Samani E, Xing Y, Martin KC, Wohlschlegel JA, Black DL. Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR.. Cell, 2016.
- Martin KC, Schuman EM. NEUROSCIENCE. Opting in or out of the network.. Science (New York, N.Y.), 2015.
- Lee JA, Damianov A, Lin CH, Fontes M, Parikshak NN, Anderson ES, Geschwind DH, Black DL, Martin KC. Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes.. Neuron, 2015.
- Ch'ng TH, DeSalvo M, Lin P, Vashisht A, Wohlschlegel JA, Martin KC. Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons.. Frontiers in molecular neuroscience, 2015.
- Kim S, Martin KC. Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome.. eLife, 2015.
- Ho VM, Dallalzadeh LO, Karathanasis N, Keles MF, Vangala S, Grogan T, Poirazi P, Martin KC. GluA2 mRNA distribution and regulation by miR-124 in hippocampal neurons.. Molecular and cellular neurosciences, 2014.
- Ch'ng TH, Uzgil B, Lin P, Avliyakulov NK, O'Dell TJ, Martin KC. Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus.. Cell, 2012.
- Meer EJ, Wang DO, Kim S, Barr I, Guo F, Martin KC. Identification of a cis-acting element that localizes mRNA to synapses.. Proceedings of the National Academy of Sciences of the United States of America, 2012.
- Ho VM, Lee JA, Martin KC. The cell biology of synaptic plasticity.. Science (New York, N.Y.), 2011.
- Ch'ng TH, Martin KC. Synapse-to-nucleus signaling.. Current opinion in neurobiology, 2011.
- Martin KC. Anchoring local translation in neurons.. Cell, 2010.
- Wang DO, Martin KC, Zukin RS. Spatially restricting gene expression by local translation at synapses.. Trends in neurosciences, 2010.
- Jeffrey RA, Ch'ng TH, O'Dell TJ, Martin KC. Activity-dependent anchoring of importin alpha at the synapse involves regulated binding to the cytoplasmic tail of the NR1-1a subunit of the NMDA receptor.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009.
- Dzudzor B, Huynh L, Thai M, Bliss JM, Nagaoka Y, Wang Y, Ch'ng TH, Jiang M, Martin KC, Colicelli J. Regulated expression of the Ras effector Rin1 in forebrain neurons.. Molecular and cellular neurosciences, 2009.
- Zhao Y, Wang DO, Martin KC. Preparation of Aplysia sensory-motor neuronal cell cultures.. Journal of visualized experiments : JoVE, 2009.
- Wang DO, Kim SM, Zhao Y, Hwang H, Miura SK, Sossin WS, Martin KC. Synapse- and stimulus-specific local translation during long-term neuronal plasticity.. Science (New York, N.Y.), 2009.
- Martin KC, Ephrussi A. mRNA localization: gene expression in the spatial dimension.. Cell, 2009.
- Shobe JL, Zhao Y, Stough S, Ye X, Hsuan V, Martin KC, Carew TJ. Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons.. Neuron, 2009.
- Lai KO, Zhao Y, Ch'ng TH, Martin KC. Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons.. Proceedings of the National Academy of Sciences of the United States of America, 2008.
- Delgado JY, Coba M, Anderson CN, Thompson KR, Gray EE, Heusner CL, Martin KC, Grant SG, O'Dell TJ. NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007.
- Poon MM, Choi SH, Jamieson CA, Geschwind DH, Martin KC. Identification of process-localized mRNAs from cultured rodent hippocampal neurons.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006.
- Zhao Y, Leal K, Abi-Farah C, Martin KC, Sossin WS, Klein M. Isoform specificity of PKC translocation in living Aplysia sensory neurons and a role for Ca2+-dependent PKC APL I in the induction of intermediate-term facilitation.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006.
- Martin KC, Zukin RS. RNA trafficking and local protein synthesis in dendrites: an overview.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006.
- Otis KO, Thompson KR, Martin KC. Importin-mediated nuclear transport in neurons.. Current opinion in neurobiology, 2006.
- Lyles V, Zhao Y, Martin KC. Synapse formation and mRNA localization in cultured Aplysia neurons.. Neuron, 2006.
- Thompson KR, Otis KO, Chen DY, Zhao Y, O'Dell TJ, Martin KC. Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway.. Neuron, 2004.
- Ormond J, Hislop J, Zhao Y, Webb N, Vaillaincourt F, Dyer JR, Ferraro G, Barker P, Martin KC, Sossin WS. ApTrkl, a Trk-like receptor, mediates serotonin- dependent ERK activation and long-term facilitation in Aplysia sensory neurons.. Neuron, 2004.
- Martin KC, Sun YE. To learn better, keep the HAT on.. Neuron, 2004.
- Martin KC. Local protein synthesis during axon guidance and synaptic plasticity.. Current opinion in neurobiology, 2004.
- Moccia R, Chen D, Lyles V, Kapuya E, E Y, Kalachikov S, Spahn CM, Frank J, Kandel ER, Barad M, Martin KC. An unbiased cDNA library prepared from isolated Aplysia sensory neuron processes is enriched for cytoskeletal and translational mRNAs.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003.
- Zhao Y, Hegde AN, Martin KC. The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening.. Current biology : CB, 2003.
- Martin KC. Synaptic tagging during synapse-specific long-term facilitation of Aplysia sensory-motor neurons.. Neurobiology of learning and memory, 2002.
- Martin KC, Kosik KS. Synaptic tagging -- who's it?. Nature reviews. Neuroscience, 2002.
- Martin KC. Arc mRNA dynamics: return to sender--the NMDA receptor provides the targeting address for Arc mRNA.. Trends in neurosciences, 2001.
- Martin KC, Barad M, Kandel ER. Local protein synthesis and its role in synapse-specific plasticity.. Current opinion in neurobiology, 2000.