Controlling Synaptogenesis

Sci. Signal.  01 Dec 2009:
Vol. 2, Issue 99, pp. ec384
DOI: 10.1126/scisignal.299ec384

Lim et al. investigated the biological functions of the brain-specific protein tyrosine phosphatase receptor–type T (PTPRT). Hippocampal neurons overexpressing wild-type PTPRT (WT-RT) showed increased numbers of dendritic spines, excitatory synapses, and inhibitory synapses compared with those expressing a control plasmid. Conversely, knockdown of PTPRT by small interfering RNA (siRNA) in neurons reduced spine density and synapse formation. Mass spectrometry of PTPRT immunoprecipitates from brain extract identified the neuroligin and neurexin families of cell adhesion proteins as PTPRT binding partners; coimmunoprecipitation assays in transfected cells showed that neuroligin-1 and neurexin-2α bound to the ectodomain of PTPRT. Incubation of neurons with purified PTPRT ectodomain decreased spine density and synapse formation, which suggests that interaction of neuroligins and neurexins with PTPRT promoted these processes. PTPRT also interacted with the tyrosine kinase Fyn, and phosphorylation of Tyr912 in the catalytic domain of PTPRT decreased its activity in vitro. Coexpression of Fyn with PTPRT prevented the increase in spine density and synapse formation seen with expression of PTPRT alone, and overexpression of a PTPRT mutant that could not be phosphorylated at Tyr912 did not increase spine density and synapse formation. Furthermore, overexpression of Fyn reduced the colocalization of neuroligin-1 with PTPRT in neurons, leading the authors to suggest that Fyn-mediated phosphorylation of PTPRT decreases its association with neuroligins, leading to reduced spine and synapse formation.

S. H. Lim, S.-K. Kwon, M. K. Lee, J. Moon, D. G. Jeong, E. Park, S. J. Kim, B. C. Park, S. C. Lee, S.-E. Ryu, D.-Y. Yu, B. H. Chung, E. Kim, P.-K. Myung, J.-R. Lee, Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn. EMBO J. 28, 3564–3578 (2009). [PubMed]