Myosin 18A is highly concentrated in dendritic spines of Purkinje neurons: possible implications for spine morphogenesis

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	CELLBIO-1

* FARE Award Winner

Authors

• M Barzik
• JA Hammer III

Abstract

Cerebellar Purkinje neurons are master regulators of body movement and coordination, and their disruption results in diseases like spinocerebellar ataxia. Myosin18A is a new member of the myosin superfamily and highly enriched in Purkinje neurons. The mouse Myo18A gene encodes two splice variants, Myo18A-α and Myo18A-β, which both possess typical myosin motor, neck, and tail domains. Myo18A-α also contains an extended N-terminus harboring a region enriched in Lysine and Glutamate (KE region), an ATP-insensitive actin-binding site, and a PDZ domain. Myo18A-α, but not Myo18A-β, localizes strongly to dendritic spines of Purkinje neurons. We found that the N-terminal extension of Myo18A-α by itself targets to spines and investigated which of its domain elements are required for spine localization. While neither the N-terminal KE region nor the PDZ domain determine spine targeting, the actin-binding site appears to control the distinctive localization of Myo18A-α. We identified two novel Myo18A splice variants that encode additional protein domains of unknown function and that also localize strongly to Purkinje neuron spines. In contrast to Myo18A-α, their N-terminal extensions alone are insufficient for spine targeting. We postulate that these novel isoforms mediate interactions with distinct downstream effectors to spatially and temporally regulate Myo18A function during neuronal development.

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