Zhou L, Yang D, Wang DJ, Xie YJ, Zhou JH, Zhou L, Huang H, Han S, Shao CY, Li HS, Zhu JJ, Qiu MS, De Zeeuw CI, Shen Y. Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination. Proc Natl Acad Sci U S A. 2015 Nov 30. pii: 201512915.

Abstract:

Protein Numb controls cell fate by interacting with a number of signaling molecules, critical for maintaining neural stem cells and neuronal development in the central nervous system. However, the function of Numb has not been studied in mature neurons. Here, we found that deletion of Numb in cerebellar Purkinje cells causes deficits in motor learning, which can be ascribed to a reduced level of synaptic metabotropic glutamate 1 receptor (mGlu1). Although Numb deficiency does not alter the expression of mGlu1-associated proteins and activity-dependent plasticity of mGlu1, it inhibits intracellular trafficking of mGlu1. To our knowledge, our work is the first to demonstrate an important function of Numb in mature neurons.