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Kelsey Martin, M.D., Ph.D.

Email Address:
kcmartin@mednet.ucla.edu

Office Address:
UCLA Biol Chem
615 Charles E Young
BOX 951737, 390-B BSRB
Los Angeles, CA 90095
UNITED STATES

Work Address:
Laboratory
615 Charles E. Young Dr. S.
Los Angeles, CA 90095
UNITED STATES

Lab Number:
(310) 794-9502
Office Phone Number:
(310)794-9507



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Department / Division Affiliations
Chair, Biological Chemistry
Professor, Psychiatry and Biobehavioral Sciences
Co-Director, UCLA-Caltech Medical Scientist Training Program
Professor, Biological Chemistry
Member, ACCESS Program: Dept. of Biological Chemistry, Access Cell and Developmental Biology Home Area, Access Neuroscience Home Area, Brain Research Institute, CTSI, Neuroscience IDP
Faculty, Center for Neurobehavioral Genetics

Research Interest:

Cell Biology of Learning-related Synaptic Plasticity

<p>Synaptic plasticity, the modification of connections in the brain by experience, is the best correlate of learning and memory in invertebrate and vertebrate animals. Long-lasting forms of synaptic plasticity have been shown to require gene expression. This means that signals must be transported from the synapse, where they are generated, to the nucleus, where they are converted into changes in gene expression. The products of gene expression must then be transported from the cell soma to the synapse to produce enduring changes in synaptic strength. My lab is interested in both aspects of communication between the synapse and the nucleus during synaptic plasticity in neurons. We study these questions in cultured Aplysia sensory-motor neurons and in cultured rodent hippocampal neurons using cell biological, molecular biological and electrophysiological techniques. Tranport of molecules from the synapse to the nucleus of neurons is particularly challenging because synapses are often very far from the cell body. We are focusing on the role of the active nuclear import pathway in mediating this transport. We find that the importin nuclear transport factors are present in distal synapses, and that distinct stimuli trigger the nuclear translocation of distinct importin alpha isoforms. We are now interested in understanding how synaptic stimulation triggers their nuclear import, in understanding the pathways whereby the importin-cargo complex travels from synapse to nucleus, and in identifying some of the cargoes themselves. </p><p> Since each neuron has a single nucleus but can form thousands of synaptic connections, the requirement for transcription during synaptic plasticity raises the question of how the products of gene expression can be targeted to alter synaptic strength at select synapses made by a given neuron. We have found that one important mechanism whereby long-lasting, transcription-dependent plasticity can occur in a synapse-specific manner involves the translation of synaptically localized mRNAs. Another mechanism involves local, regulated degradation of proteins via the ubiquitin proteasome pathway. We are using a variety of molecular, cell biological and pharmacological approaches to identify dendritically localized mRNAs, to study the regulated translation of these mRNAs, and to study the role of local protein degradation during synaptic plasticity.</p>

Bio:

Kelsey Martin, Professor in the Department of Biological Chemistry, Eleanor Leslie Term Chair in Innovative Brain Research, and Co-Director of the UCLA-Caltech Medical Scientist Training Program (MSTP), is interested in the molecular and cell biology of learning and memory. Her lab studies long-term synaptic plasticity, the process whereby neurons change the strength and number of their synaptic connections with experience. Long-term forms of synaptic plasticity, like long-term memory, require new gene expression. The Martin lab focuses on two questions that emerge from this requirement: 1) how are signals received at distal synapses relayed to the nucleus to turn on transcription? and 2) how can gene expression be spatially restricted within the neuron to allow synapse-specific forms of transcription-dependent plasticity? They study these questions using two model systems of learning-related synaptic plasticity: Aplysia sensory-motor synapses and rodent hippocampal synapses, using a combination of electrophysiology, biochemistry, cell and molecular biology. In 2004, the Martin lab discovered a role for importin-mediated active nuclear transport in carrying signals from the synapse to the nucleus during long-term synaptic plasticity. Current efforts are focused on identifying the synaptically-localized protein cargoes of importins and on understanding the cell biological pathway underlying this long-distance retrograde transport. In 1997, Kelsey Martin discovered that synapse-specific forms of long-term plasticity require translation of localized mRNAs at the synapse. The Martin lab has since identified a large population of mRNAs that are present in neurites of Aplysia sensory neurons and and dendrites of rodent hippocampal neurons. Using a combination of in situ hybridization, live cell imaging of RNA and translational reporters, siRNA-mediated gene silencing and electrophysiological recording, they are investigating the mechanisms underlying mRNA localization and regulated translation in neurons as well as the function of this form of regulated gene expression during synapse formation and synaptic plasticity. The goal of these studies is to understand how the brain forms and stores memories, and to provide insights into the pathophysiology of disorders in which learning and memory are impaired.

Publications:

Ch'ng Toh Hean, Uzgil Besim, Lin Peter, Avliyakulov Nuraly K, O'Dell Thomas J, Martin Kelsey C Activity-Dependent Transport of the Transcriptional Coactivator CRTC1 from Synapse to Nucleus. Cell. 2012; 150(1): 207-21.
Meer Elliott J, Wang Dan Ohtan, Kim Sangmok, Barr Ian, Guo Feng, Martin Kelsey C 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; 109(12): 4639-44.
Ch'ng Toh Hean, Martin Kelsey C Synapse-to-nucleus signaling. Current opinion in neurobiology. 2011; 21(2): 345-52.
Ho Victoria M, Lee Ji-Ann, Martin Kelsey C The cell biology of synaptic plasticity. Science (New York, N.Y.). 2011; 334(6056): 623-8.
Martin Kelsey C Anchoring local translation in neurons. Cell. 2010; 141(4): 566-8.
Dzudzor Bartholomew, Huynh Lucia, Thai Minh, Bliss Joanne M, Nagaoka Yoshiko, Wang Ying, Ch'ng Toh Hean, Jiang Meisheng, Martin Kelsey C, Colicelli John Regulated expression of the Ras effector Rin1 in forebrain neurons. Molecular and cellular neurosciences. 2010; 43(1): 108-16.
Wang Dan Ohtan, Martin Kelsey C, Zukin R Suzanne Spatially restricting gene expression by local translation at synapses. Trends in neurosciences. 2010; 33(4): 173-82.
Jeffrey Rachel A, Ch'ng Toh Hean, O'Dell Thomas J, Martin Kelsey C 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. 2009; 29(50): 15613-20.
Zhao Yali, Wang Dan O, Martin Kelsey C Preparation of Aplysia sensory-motor neuronal cell cultures. Journal of Visualized Experiments. 2009; 324(28): .
Wang Dan Ohtan, Kim Sang Mok, Zhao Yali, Hwang Hongik, Miura Satoru K, Sossin Wayne S, Martin Kelsey C Synapse- and stimulus-specific local translation during long-term neuronal plasticity. Science (New York, N.Y.). 2009; 324(5934): 1536-40.
Shobe Justin L, Zhao Yali, Stough Shara, Ye Xiaojing, Hsuan Vickie, Martin Kelsey C, Carew Thomas J Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons. Neuron. 2009; 61(1): 113-25.
Martin Kelsey C, Ephrussi Anne mRNA localization: gene expression in the spatial dimension. Cell. 2009; 136(4): 719-30.
Lai Kwok-On, Zhao Yali, Ch'ng Toh Hean, Martin Kelsey C 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; 105(44): 17175-80.
Delgado Jary Y, Coba Marcelo, Anderson Christopher N G, Thompson Kimberly R, Gray Erin E, Heusner Carrie L, Martin Kelsey C, Grant Seth G N, O'Dell Thomas J NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840. The Journal of Neuroscience. 2007; 27(48): 13210-21.
Poon Michael M, Choi Sang-Hyun, Jamieson Christina A M, Geschwind Daniel H, Martin Kelsey C Identification of process-localized mRNAs from cultured rodent hippocampal neurons. The Journal of Neuroscience. 2006; 26(51): 13390-9.
Otis Klara Olofsdotter, Thompson Kimberly R, Martin Kelsey C Importin-mediated nuclear transport in neurons. Current Opinion in Neurobiology. 2006; 16(3): 329-35.
Zhao Yali, Leal Karina, Abi-Farah Carole, Martin Kelsey C, Sossin Wayne S, Klein Marc 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. 2006; 26(34): 8847-56.
Martin Kelsey C, Zukin R Suzanne RNA trafficking and local protein synthesis in dendrites: an overview. The Journal of Neuroscience. 2006; 26(27): 7131-4.
Lyles, V., Zhao, Y. and Martin, K.C. Synapse formation and mRNA localization in Aplysia sensory-motor neurons. Neuron 2006; 49: 349-356.
Lyles Vlasta, Zhao Yali, Martin Kelsey C Synapse formation and mRNA localization in cultured Aplysia neurons. Neuron. 2006; 49(3): 349-56.
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; 44(4): 715-28.
Ormond Jake, Hislop Jonathan, Zhao Yali, Webb Neil, Vaillaincourt Francois, Dyer John R, Ferraro Gino, Barker Phil, Martin Kelsey C, Sossin Wayne S ApTrkl, a Trk-like receptor, mediates serotonin- dependent ERK activation and long-term facilitation in Aplysia sensory neurons. Neuron. 2004; 44(4): 715-28.
Martin Kelsey C Local protein synthesis during axon guidance and synaptic plasticity. Current opinion in neurobiology. 2004; 14(3): 305-10.
Martin, KC Local protein synthesis during axon guidance and synaptic plasticity. Current Opinion in Neurobiology. . 2004; 14(3): 305-10.
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; 44(6): 997-1009.
Thompson Kimberly R, Otis Klara Olofsdotter, Chen Dillon Y, Zhao Yali, O'Dell Thomas J, Martin Kelsey C Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron. 2004; 44(6): 997-1009.
Martin, K.C. and Sun, Y.I To Learn Better, Keep Your HAT On. Neuron 2004; 42: 879-881.
Martin Kelsey C, Sun Yi E To learn better, keep the HAT on. Neuron. 2004; 42(6): 879-81.
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. . 2003; 23(28): 9409-17.
Moccia Robert, Chen Dillon, Lyles Vlasta, Kapuya Estreya, E Yaping, Kalachikov Sergey, Spahn Christian M T, Frank Joachim, Kandel Eric R, Barad Mark, Martin Kelsey C 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; 23(28): 9409-17.
Zhao, Y Hegde, AN Martin, KC The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening. Current Biology. 2003; 13(11): 887-98.
Zhao Yali, Hegde Ashok N, Martin Kelsey C The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening. Current biology : CB. 2003; 13(11): 887-98.
Martin, K.C., and Kosik, K.S Synaptic Tagging - Who's it?. Nature Neurosci. Rev 2002; 10: 813-820.
Martin Kelsey C, Kosik Kenneth S Synaptic tagging -- who's it?. Nature reviews. Neuroscience. 2002; 3(10): 813-20.
Martin Kelsey C Synaptic tagging during synapse-specific long-term facilitation of Aplysia sensory-motor neurons. Neurobiology of learning and memory. 2002; 78(3): 489-97.
Martin, KC Synaptic tagging during synapse-specific long-term facilitation of Aplysia sensory-motor neurons. Neurobiology of Learning and Memory. . 2002; 78(3): 489-97.
Patterson, S.L., Pittenger, C., Morozov, A., Martin, K.C., Scanlin, H., Drake, C., and Kandel, E.R Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase. Neuron 2001; 32: 123-140.
Huang, YY Martin, KC Kandel, ER Both protein kinase A and mitogen-activated protein kinase are required in the amygdala for the macromolecular synthesis-dependent late phase of long-term potentiation. The Journal of Neuroscience. . 2000; 20(17): 6317-25.
Martin, KC Barad, M Kandel, ER Local protein synthesis and its role in synapse-specific plasticity. Current Opinion in Neurobiology. . 2000; 10(5): 587-92.
Martin, K.C., Bartsch, D., Bailey, C.H. and Kandel,E.R. Molecular mechanisms underlying learning-related long-lasting synaptic plasticity. The New Cognitive Neurosciences 2000; 2nd edition: 121-137.
Casadio, A.*, Martin, K.C.*, et al. A novel, transient form of CREB-mediated long-term facilitation that is neuron-wide and can be stabilized at specific synapses by local rapamycin-sensitive protein synthesis. Cell 1999; 99: 221-237.
Winder, D.G., Martin, K.C., Muzzio, I., Rohrer, D., Chruscinski, A., Kobilka, B. and Kandel, E.R. ERK plays a novel role in the induction of LTP by theta frequency stimulation and its regulation by beta-adrenergic receptors in CA1 pyramidal cells. Neuron 1999; 24: 715-726.
Martin, KC Michael, D Rose, JC Barad, M Casadio, A Zhu, H Kandel, ER MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia. Neuron. . 1997; 18(6): 899-912.
Martin, KC Casadio, A Zhu, H Yaping, E Rose, JC Chen, M Bailey, CH Kandel, ER Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage. Cell. . 1997; 91(7): 927-38.
Martin, KC Kandel, ER Cell adhesion molecules, CREB, and the formation of new synaptic connections. Neuron. . 1996; 17(4): 567-70.
Skehel, PA Martin, KC Kandel, ER Bartsch, D A VAMP-binding protein from Aplysia required for neurotransmitter release. Science. . 1995; 269(5230): 1580-3.
Martin, KC Hu, Y Armitage, BA Siegelbaum, SA Kandel, ER Kaang, BK Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle release in Aplysia neurons. Proceedings of the National Academy of Sciences of the United States of America. . 1995; 92(24): 11307-11.
Martin, K Helenius, A Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell. . 1991; 67(1): 117-30.
Martin, K Helenius, A Transport of incoming influenza virus nucleocapsids into the nucleus. Journal of Virology. . 1991; 65(1): 232-44.