BBS Faculty Member - Joshua Kaplan

Joshus Kaplan

Department of Neurobiology
Department of Molecular Biology

Massachusetts General Hospital
Simches Research Ctr, 7
185 Cambridge St.
Boston, MA 02114
Tel: 617-726-5900
Fax: 617-726-5949
Email: kaplan@molbio.mgh.harvard.edu
Lab Members: 6 postdoctoral fellows, 3 graduate students
Visit my lab page here.



Work in my lab is focused on understanding how signals in the brain lead to particular patterns of behavior. We utilize a combination of behavioral, genetic, biochemical, imaging, and electrophysiological techniques to study signaling in the brain of the worm C. elegans. Current projects include:

Analysis of synaptic defects caused mutations linked to autism. The synaptic adhesion molecules Neurexin and Neuroligin promote synapse formation and maturation and are linked to autism. We recently showed that the worm Neurexin and Neuroligin mediate a retrograde synaptic signal that regulates the kinetics of neurotransmitter release. We are now analyzing other autism linked genes to determine if they also play a role in this retrograde signal, or if they have similar effects on the kinetics of synaptic responses.

Activity-dependent plasticity. We recently identified and are characterizing several forms of activity-dependent synaptic plasticity at the NMJ. For example, we identified a neuropeptide that induces a presynaptic form of potentiation. This peptide functions as part of a mechanosensory reflex that links muscle contraction to changes in ACh secretion at the NMJ. We also discovered a form of post-synaptic potentiation that occurs only in mutants lacking a cell surface Ig domain protein (IgSF). Thus, this IgSF protein prevents inappropriate potentiation of synapses, acting as an “antiplasticity” molecule.

Regulation of insulin and neuropeptide secretion. Insulin secretion, and its misregulation, plays a pivotal role in aging, diabetes, and obesity. We have developed assays for insulin secretion in intact worms. Using these assays, we are analyzing mechanisms regulating insulin secretion, and are pursuing genetic screens to identify genes required for insulin secretion.

microRNA regulation of synaptic transmission and synaptic development. We showed that the miRNA miR-1 alters synaptic transmission by regulating a retrograde signal from muscle that inhibits neurotransmitter release from motor neurons. Other miRNAs (the Let-7 family) regulate the timing of GABA synapse remodeling. We are currently characterizing miR-1 and Let-7 targets involved in these processes.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Hu, Z., Hom, S., Kudze, T., Tong, X.-J., Choi, S., Aramuni, G., Zhang, W., and Kaplan, J.M. (2012). Neurexin and Neuroligin mediate retrograde synaptic inhibition in C. elegans. Science in press.

Thompson-Peer, K., Bai, J., Hu, Z., and Kaplan, J. (2012). HBL-1 patterns synaptic remodeling in C. elegans. Neuron
73, 453-465.

Babu, K., Hu, Z., Chien, S. C., Garriga, G., and Kaplan, J. M. (2011). The Immunoglobulin Super Family Protein RIG-3 Prevents Synaptic Potentiation and Regulates Wnt Signaling. Neuron
71, 103-116.

Hu, Z., Pym, E. C., Babu, K., Vashlishan Murray, A. B., and Kaplan, J. M. (2011). A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron
71, 92-102.

Bai, J., Hu, Z., Dittman, J. S., Pym, E. C., and Kaplan, J. M. (2010). Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell
143, 430-441.

Simon, D. J., Madison, J. M., Conery, A. L., Thompson-Peer, K. L., Soskis, M., Ruvkun, G. B., Kaplan*, J. M., and Kim, J. K. (2008). The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions. Cell
133, 903-915. *Corresponding author



© 2013 by the President and Fellows of Harvard College