Published online July 30, 2007
doi:10.1083/jcb.200609146
The Journal of Cell Biology, Vol. 178, No. 3, 503-516
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Rosário et al.
The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42
Marta Rosário,
Renate Franke,
Christien Bednarski, and
Walter Birchmeier
Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
Correspondence to Marta Rosário: m.rosario{at}mdc-berlin.de
Neuronal differentiation involves the formation and extension of neuronal processes. We have identified a novel regulator of neurite formation and extension, the neurite outgrowth multiadaptor, NOMA-GAP, which belongs to a new family of multiadaptor proteins with RhoGAP activity. We show that NOMA-GAP is essential for NGF-stimulated neuronal differentiation and for the regulation of the ERK5 MAP kinase and the Cdc42 signaling pathways downstream of NGF. NOMA-GAP binds directly to the NGF receptor, TrkA, and becomes tyrosine phosphorylated upon receptor activation, thus enabling recruitment and activation of the tyrosine phosphatase SHP2. Recruitment of SHP2 is required for the stimulation of neuronal process extension and for sustained activation of ERK5 downstream of NOMA-GAP. In addition, we show that NOMA-GAP promotes neurite outgrowth by tempering activation of the Cdc42/PAK signaling pathway in response to NGF. NOMA-GAP, through its dual function as a multiadaptor and RhoGAP protein, thus plays an essential role downstream of NGF in promoting neurite outgrowth and extension.
Abbreviations used in this paper: DRG, dorsal root ganglia; GAP, GTPase activating protein; NOMA-GAP, neurite outgrowth multiadaptor RhoGAP.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
