Geon The Roles of Tubulin and CRMP2 in Neuronal Excitability

 

Abstract

This paper shows that tubulin may modulate excitability at dendritic spines, axon terminals and the axon initial segment (AIS). Tubulin is a highly negatively charged molecule. Its close contact with the neuronal membrane would be able to inhibit the generation of action potentials. At dendritic spines, tubulin has been demonstrated to interact with NMDA receptors (NMDARs). The collapsin response mediator protein 2 (CRMP2) interacts with both tubulin and NMDARs. Therefore, CRMP2 may enhance the tubulin-NMDAR binding, thereby modulating synaptic strength. The antibodies against CRMP2 was shown to induce amnesia, which underscores the importance of CRMP2 in memory retrieval. 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. This could be the mechanism underlying seizure termination.

 

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