Molecular Medicine Israel

Newly discovered NYAP phosphoprotein family that links PI3K to WAVE1 signalling in neurons

The EMBO Journal (2011) 30, 4739 – 4754

The signaling factor phosphoinositide 3-kinase (PI3K) participates in numerous essential cellular processes, including regulation of the growth and structural integrity of neurons. Remarkably little is known about how PI3K acts in the brain, but research from University of Tokyo researcher Tadashi Yamamoto and colleagues has uncovered a trio of proteins that appear to be primary partners for this factor1.

These molecules, which the researchers have dubbed the ‘neuronal tyrosine-phosphorylated adaptor for PI3K’ (NYAP) family, are not essential for survival. However, mice lacking all three NYAPs exhibit abnormally small brains, a phenotype that appears to arise from the failure of neurons to fully extend synapse-forming neurites.

Yamamoto and colleagues found that the NYAPs essentially act as a bridge between PI3K and various components of the WAVE1 protein complex. WAVE1 regulates the structure of the cytoskeleton, a latticework of protein filaments that help define cell shape and contribute to growth and movement.

The researchers demonstrated that contactin, a protein with a role in neuronal circuit building, specifically induces formation of the PI3K–NYAP–WAVE1 complex, which in turn promotes the cytoskeletal rearrangements necessary for neurite extension. Given that mutations near human NYAP genes have been tentatively associated with autism, these genes could potentially play a prominent role in the brain’s functional connectivity.


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