New insights into the mechanism of dynein motor regulation by lissencephaly-1

eLife

Matthew G Marzo¹  Steven M Markus¹  Richard J McKenney² 

[1] Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, United States;Department of Molecular and Cellular Biology, University of California, Davis, Davis, United States;

关键词: dynein;    LIS1;    lissencephaly;    dynactin;    nuclear migration;    neuronal migration;   

DOI  :  10.7554/eLife.59737

来源: DOAJ

【 摘 要 】

Lissencephaly (‘smooth brain’) is a severe brain disease associated with numerous symptoms, including cognitive impairment, and shortened lifespan. The main causative gene of this disease – lissencephaly-1 (LIS1) – has been a focus of intense scrutiny since its first identification almost 30 years ago. LIS1 is a critical regulator of the microtubule motor cytoplasmic dynein, which transports numerous cargoes throughout the cell, and is a key effector of nuclear and neuronal transport during brain development. Here, we review the role of LIS1 in cellular dynein function and discuss recent key findings that have revealed a new mechanism by which this molecule influences dynein-mediated transport. In addition to reconciling prior observations with this new model for LIS1 function, we also discuss phylogenetic data that suggest that LIS1 may have coevolved with an autoinhibitory mode of cytoplasmic dynein regulation.

【 授权许可】

Unknown