Peri Kurshan, Ph.D.
Assistant Professor, Dominick P. Purpura Department of Neuroscience
(neuroscience category)
Synaptic development, synaptogenesis, synapse function, molecular neuroscience, cellular neurobiology, synaptic cell biology, C. elegans, genetics, development
Studying synaptic development and function using C. elegans
Defects in the proper development and function of synapses lead to neurodevelopmental disorders such as Autism and Intellectual Disability, however the molecular mechanisms underlying these processes are still largely unknown. We use the nematode C. elegans, which has a simple and stereotyped nervous system and whose connectome has been fully mapped out, to investigate the conserved molecular mechanisms of synapse development. In particular, we study how presynaptic components including cell adhesion molecules, active zone scaffold proteins, calcium channels and synaptic vesicles arrive at the synapse and form a mature and fully functional presynaptic compartment. We combine the power of worm genetics with high resolution imaging and optical physiology readouts to elucidate the role of key molecules. These approaches have led to discoveries suggesting that the role of synaptic cell adhesion molecules such as Neurexin may be different than initially hypothesized, as we have shown that its role in presynaptic development is independent of extracellular activation and downstream of other initiating factors.
Selected Publications
Synaptogenic pathways. Kurshan PT, Shen K. Curr Opin Neurobiol. 2019 Apr 12;57:156–162. doi: 10.1016/j.conb.2019.03.005. [Epub ahead of print] Review.
g-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis. Kurshan PT, Merrill SA, Dong Y, Ding C, Hammarlund M, Bai J, Jorgensen EM, Shen K. Neuron. 2018 Oct 10;100(1):150–166.e4. doi: 10.1016/j.neuron.2018.09.007.
Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release. Xuan Z, Manning L, Nelson J, Richmond JE, Colón-Ramos DA, Shen K, Kurshan PT. Elife. 2017 Nov 21;6. pii: e29276. doi: 10.7554/eLife.29276. Free PMC Article
Deep phenotyping unveils hidden traits and genetic relations in subtle mutants. San-Miguel A, Kurshan PT, Crane MM, Zhao Y, McGrath PT, Shen K, Lu H. Nat Commun. 2016 Nov 23;7:12990. doi: 10.1038/ncomms12990. Free PMC Article
Prevalent presence of periodic actin-spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species. He J, Zhou R, Wu Z, Carrasco MA, Kurshan PT, Farley JE, Simon DJ, Wang G, Han B, Hao J, Heller E, Freeman MR, Shen K, Maniatis T, Tessier-Lavigne M, Zhuang X. Proc Natl Acad Sci U S A. 2016 May 24;113(21):6029–34. doi: 10.1073/pnas.1605707113. Epub 2016 May 9. Free PMC Article
Regulation of synaptic extracellular matrix composition is critical for proper synapse morphology. Kurshan PT, Phan AQ, Wang GJ, Crane MM, Lu H, Shen K. J Neurosci. 2014 Sep 17;34(38):12678-89. doi: 10.1523/jneurosci.1183–14.2014. Free PMC Article
Autonomous screening of C. elegans identifies genes implicated in synaptogenesis. Crane MM, Stirman JN, Ou CY, Kurshan PT, Rehg JM, Shen K, Lu H. Nat Methods. 2012 Oct;9(10):977–80. doi: 10.1038/nmeth.2141. Free PMC Article
Dendritic patterning: three-dimensional position determines dendritic avoidance capability. Kurshan PT, Shen K. Curr Biol. 2012 Mar 20;22(6):R192–4. doi: 10.1016/j.cub.2012.02.017. Preview. Free Article
Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions. Kurshan PT, Oztan A, Schwarz TL. Nat Neurosci. 2009 Nov;12(11):1415–23. doi: 10.1038/nn.2417. Free PMC Article
Mutations in a Drosophila alpha2delta voltage-gated calcium channel subunit reveal a crucial synaptic function. Dickman DK*, Kurshan PT*, Schwarz TL. J Neurosci. 2008 Jan 2;28(1):31-8. doi: 10.1523/jneurosci.4498-07.2008. Free Article
A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Pack-Chung E, Kurshan PT, Dickman DK, Schwarz TL. Nat Neurosci. 2007 Aug;10(8):980–9.