New Regulator of Dendrite and Synapse Formation

Science's STKE  14 Sep 2004:
Vol. 2004, Issue 250, pp. tw323
DOI: 10.1126/stke.2502004tw323

Two papers from Shi and colleagues describe a new receptor-like molecule that functions in formation and maturation of dendrites, the specialized structures on neurons where the cells receive input from other neurons. Having noted genetic evidence from Drosophila that a protein from the immunoglobulin superfamily appeared to function in formation of dendrites, the authors searched for similar proteins in vertebrates and identified a mouse protein they named Dasm1, short for dendrite arborization and synapse maturation 1. In cultured rat hippocampal neurons, loss of Dasm1 after treatment of cells with RNA interference (RNAi) inhibited outgrowth of dendrites but not that of axons. To examine later stages of synapse formation, the authors prepared hippocampal slices from 8-day-old rats and introduced RNAi or the dominant-negative form of Dasm1 with a gene gun. In this case, inhibition of Dasm1 function reduced acquisition of signaling through AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, which is normally associated with synapse maturation. The authors also identified two possible binding partners for Dasm1 in yeast two-hybrid assays or by immunoprecipitation from transfected cells. These proteins, Shank (Src homology 3 domain- and ankyrin repeat-containing protein) and S-SCAM (synaptic scaffolding molecule), were previously implicated in regulation of synaptic function. Therefore, Dasm1 appears to transmit extracellular signals to postsynaptic neurons and, thus, to regulate cytoskeletal organization and synaptic expression of neurotransmitter receptors that mediate dendrite formation and formation of functional mature synapses.

S.-H. Shi, D. N. Cox, D. Wang, L. Y. Jan, Y.-N. Jan, Control of dendrite arborization by an Ig family member, dendrite arborization and synapse maturation 1 (Dasm1). Proc. Natl. Acad. Sci. U.S.A. 101, 13341-13345 (2004). [Abstract] [Full Text]

S.-H. Shi, T. Cheng, L. Y. Jan, Y.-N. Jan, The immunoglobin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation. Proc. Natl. Acad. Sci. U.S.A. 101, 13346-13351 (2004). [Abstract] [Full Text]