Scaffold protein X11-alpha interacts with kalirin-7 in dendrites and recruits it to Golgi outposts [Neurobiology]

November 5th, 2014 by Jones, K. A., Eng, A. G., Raval, P., Srivastava, D. P., Penzes, P.

Pyramidal neurons in the mammalian forebrain receive their synaptic inputs through their dendritic trees, and dendritic spines are the sites of most excitatory synapses. Dendritic spine structure is important for brain development and plasticity. Kalirin-7 is a guanine-nucleotide exchange factor (GEF) for the small GTPase Rac1, and is a critical regulator of dendritic spine remodeling. The subcellular localization of kalirin-7 is thought to be important for regulating its function in neurons. A yeast 2-hybrid screen has identified the adaptor protein X11α as an interacting partner of kalirin-7. Here we show that kalirin-7 and X11α form a complex in the brain, and this interaction is mediated by the C-terminus of kalirin-7. Kalirin-7 and X11α colocalize at excitatory synapses in cultured cortical neurons. Using time-lapse imaging of fluorescence recovery after photobleaching, we show that X11α is present in a mobile fraction of the postsynaptic density. X11α also localizes to Golgi outposts in dendrites, and its overexpression induces the removal of kalirin-7 from spines and accumulation of kalirin-7 in Golgi outposts. In addition, neurons overexpressing X11α displayed thinner spines. These data support a novel mechanism of regulation of kalirin-7 localization and function in dendrites, providing insight into signaling pathways underlying neuronal plasticity. Dissecting the molecular mechanisms of synaptic structural plasticity will improve our understanding of neuropsychiatric and neurodegenerative disorders, as kalirin-7 has been associated with schizophrenia and Alzheimer′s disease.