Geon The Roles of Tubulin and CRMP2 in Neuronal Excitability Papers



This paper shows that tubulin may modulate excitability at dendritic spines, axon terminals and the axon initial segment (AIS). At dendritic spines, the tubulin heterodimer may form a complex (called "CABT" complex) with collapsin response mediator protein 2 (CRMP2) to block GluN2B-containing NMDA receptors (NMDARs). The blockade of NMDARs by CABT could be the underlying mechanism for silent neurons which are prevalent in the hippocampus and neocortex. This hypothesis is consistent with several intrinsic properties of silent neurons. It also explains the antiepileptic action of lacosamide (LCM), which has been demonstrated to interact with CRMP2. At the axon terminals, tubulin may cooperate with parkin and leucine rich repeat kinase 2 (LRRK2) - two proteins implicated in Parkinson's disease. Parkin is an E3 ubiquitin ligase, capable of promoting tubulin degradation. LRRK2 is a large protein, whose binding with tubulin may prevent tubulin from entering the actin/spectrin layer beneath the neuronal membrane, thus facilitating synaptic transmission. At AIS, intensive neural activity would cause Ca2+ overload, which can induce microtubule depolymerization to produce free tubulin, consequently inhibiting neuronal firing.


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