Of Neurons and Microtubules: Tales from the Tubulin Code

Francesca Bartolini, PhD
Associate Professor of Pathology and Cell Biology
Columbia University

The Bartolini Lab investigates the role of microtubule dynamics and tubulin post-translational modifications in neuronal physiology and at the onset of neurodegenerative and neuropathic disease.

Neurons possess extensive tubulin post-translational modifications (PTMs) that are associated with microtubule (MT) longevity, and analyses of mammalian brain and cultured neurons demonstrate enrichment of detyrosinated, acetylated, poly-glutamylated and D2-tubulin subunits. These tubulin PTMs are implicated in the regulation of MT associated proteins (known as MAPs), MT severing enzymes, and binding to motors.

Synaptic activation also locally regulates tubulin PTMs associated with MT stability. In addition to stable MTs, emerging studies indicate that dynamic MTs, typically deprived of tubulin PTMs, play key roles in neuronal function. Dynamic MTs polymerize from dendritic shafts into spines, and signaling through neurotransmitter receptors and local calcium entry regulate this process. Invasion of dendritic spines by dynamic MTs can in return affect spine morphology and function by regulating myosin- and kinesin-paired cargo dynamics. Furthermore, presynaptic dynamic MTs are necessary for the delivery of synaptic vesicles to their appropriate sites, and may mediate storage and/or docking /fusion of vesicles at the active zone.