Volume 1122, Issue 1 p. 313-329

Rab-Mediated Endocytosis

Linking Neurodegeneration, Neuroprotection, and Synaptic Plasticity?

ANDRIUS BASKYS

ANDRIUS BASKYS

Memory Disorders Program, VA HCS Long Beach, Long Beach, California, USA

Southern California Institute for Research and Education (SCIRE), Long Beach, California, USA

Psychiatry and Human Behavior, University of California at Irvine, Irvine, California, USA

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ILDAR BAYAZITOV

Corresponding Author

ILDAR BAYAZITOV

Southern California Institute for Research and Education (SCIRE), Long Beach, California, USA

Psychiatry and Human Behavior, University of California at Irvine, Irvine, California, USA

Address for correspondence: A. Baskys, M.D., Ph.D., Memory Disorders Program, VA HCS Long Beach, 5901 E. 7th St. 06/116 A, Long Beach, CA 90822. [email protected]

d Present address: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

fPresent address: Experimental Center, Xuan-wu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.

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ERCHENG ZHU

ERCHENG ZHU

Southern California Institute for Research and Education (SCIRE), Long Beach, California, USA

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LIWEI FANG

LIWEI FANG

Southern California Institute for Research and Education (SCIRE), Long Beach, California, USA

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RONG WANG

Corresponding Author

RONG WANG

Experimental Center, Xuan-wu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China

Address for correspondence: A. Baskys, M.D., Ph.D., Memory Disorders Program, VA HCS Long Beach, 5901 E. 7th St. 06/116 A, Long Beach, CA 90822. [email protected]

d Present address: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

fPresent address: Experimental Center, Xuan-wu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China.

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First published: 10 December 2007
Citations: 20

Abstract

Rab proteins are small GTPases involved in endocytosis and recycling of cell surface molecules. Recently they have been implicated in the etiopathogenesis of several neurodegenerative disorders including Alzheimer's and Lewy body disease. In experiments on organotypic hippocampal cultures, upregulation of Rab protein family member Rab5b after group I metabotropic glutamate receptor (mGluR) stimulation was associated with reduced neuronal vulnerability to excitotoxic injury. This mGluR-mediated neuroprotection was abolished by antisense-induced deficiency of Rab5b. Electrophysiological measurements of excitatory synaptic transmission in the Schaffer collateral–CA1 pathway revealed that mGluR activation that induces neuroprotection also induced long-term depression (LTD) of synaptic transmission. Similar to the neuroprotection, Rab5b deficiency abolished dihydroxyphenylglycine-induced LTD. Together, these findings support the idea that Rab proteins, and the Rab5b protein in particular, may provide a link between neurodegenerative disease, neuroprotection, and synaptic plasticity, as well as possibly being a useful target for pharmacological interventions.