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Nuclear export of HDAC1 is induced by pathological conditions and is essential for the onset of axonal damage

Jin Young Kim
M.S., 2001
Sungkyunkwan University
South Korea

Thesis Advisor: Dr. Patrizia Casaccia-Bonnefil

Graduate Program of Neuroscience

RWJMS Research Tower
Room V-10
Busch Campus

Tuesday, April 21, 2009
10:00 am


Histone deacetylase 1 (HDAC1) is a well characterized nuclear enzyme involved in transcriptional repression. We demonstrate here that in response to pathological stimuli, HDAC1 is exported from the nucleus to the axon, where it induces morphological and functional changes. The cytosolic localization of HDAC1 is preceded by binding tos the nuclear receptor CRM-1 and followed by neuritic swellings that could be prevented either by silencing HDAC1 or blocking its nuclear export. Over-expression of a mutant HDAC1 that constitutively accumulates in the cytoplasm is sufficient to induce neuritic beading in untreated neurons. Proteomic identification of HDAC1-binding proteins in neurons treated with toxic stimuli and in extracts from demyelinated brain regions reveals axonal motor proteins and cytoskeletal components. These proteins interact with HDAC1, but not with other isoforms, only in response to pathological conditions, thereby suggesting a previously unrecognized role for nucleo-cytoplasmic export of HDAC1 in axonal damage.

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