GITing Actin Regulators to the Synapse

Science's STKE  22 Apr 2003:
Vol. 2003, Issue 179, pp. tw160-TW160
DOI: 10.1126/stke.2003.179.tw160

Patients with nonsyndromic mental retardation often have mutations in genes that regulate the Rho family of small guanosine triphosphatases (GTPases), which regulates actin. This has raised the question of whether the cellular basis of cognitive function is linked to Rho-based signaling pathways that modulate the formation and stability of neuronal synapses and actin-rich, synapse-bearing dendritic spines. Zhang et al. have determined that a signaling adaptor protein called G protein-coupled receptor kinase-interacting protein (GIT) 1 is enriched in synapses of cultured hippocampal neurons. A domain within GIT1 was identified that not only specifies synapse targeting, but also harbors a binding site for PIX, a guanine nucleotide exchange factor for the Rho-related protein Rac. Expression of a dominant-negative GIT1 mutant inhibited endogenous GIT1 and PIX localization to synapses, blocked normal dendritic spine formation, and caused a decrease in the total number of synapses. The authors propose that GIT1-based targeting of actin regulators like Rac and PIX may underlie the dynamic properties of synapse and dendritic spine formation that are linked to cognition.

H. Zhang, D. J. Webb, H. Asmussen, A. F. Horwitz, Synapse formation is regulated by the signaling adaptor GIT1. J. Cell Biol. 161, 131-142 (2003). [Abstract] [Full Text]