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Michael Silverman"FAT and happy: fast axonal transport in healthy and diseased neurons"

Abstract :


Transport of membrane-bound organelles is essential for neuronal function and survival.
A critical cellular cargo, called dense-core vesicles (DCVs), is responsible for the transport and secretion of a large group of neuropeptides, e.g. brain derived neurotrophic factor (BDNF), that are required for development, learning, memory, and neuronal survival. These molecules are packaged into DCVs in the Golgi apparatus then delivered to distal release sites via microtubule-based transport. Importantly, disruption of neuronal transport, including DCV transport, is a hallmark of neurodegenerative diseases such as Alzheimer's and Parkinson's. Despite the importance of DCVs in neuronal function, little is known about the mechanisms mediating their transport. The focus of my lab is to characterize DCV transport and identify the motor proteins required for their transport to distal sites of release. Additionally, recent work is geared towards understanding how soluble amyloid beta oligomers implicated in Alzheimer's disease disrupt fast axonal transport. To address these questions we employ live-cell imaging to directly observe organelle transport in primary cultured hippocampal neurons.

Selected publications

Lo, K.Y. , Kuzmin A. , Unger, S. M., Petersen, J.D., and Silverman, M.A.. KIF1A is the primary anterograde motor protein required for the axonal transport of dense-core vesicles in cultured hippocampal neurons. Neuroscience Letters. 2011 Mar 24;491(3):168-73.

Silverman MA*, Kaech S*, E. M. Ramser, Lu X, Lasarev MR, Nagalla S, and Banker G, (* equal authorship) Expression of kinesin superfamily genes in cultured hippocampal neurons. Cytoskeleton, 2010 Dec; 67(12):784-95.

Decker H, Lo KY, Unger SM, Ferreira ST, Silverman MA. Aß oligomers disrupt axonal transport via an N-methyl-D-aspartate receptor-dependent mechanism in primary cultured hippocampal neurons. Journal of Neuroscience. 2010 Jul 7;30(27):9166-71.

Scientific focus :

The primary goal of our lab is to understand how protein transport underlies nerve cell form and function. This work is significant because neurons are dependent upon very precise localization of proteins to support their ability to send and receive information, which directly relates to how animals learn and respond to their environment.

By understanding the basic cellular mechanisms and development of individual neurons, we can better understand how the nervous system develops in an entire animal. Furthermore, disruption of the basic transport mechanisms in the cell are hallmarks of neurodegenerative diseases such as Alzheimer’s and Huntington’s disease.

Jennifer Petersen