Chemical genetic-mediated spatial regulation of protein expression in neurons reveals an axonal function for wld S

Michael S. Cohen, Ananda K. Ghosh, Hyung Joon Kim, Noo Li Jeon, Samie R. Jaffrey

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The degeneration of axons is the underlying pathological process of several neurological disorders. The Wallerian degeneration (Wld S) slow protein, which is primarily nuclear, markedly inhibits axonal degeneration. Contradictory models have been proposed to explain its mechanism, including a role in the nucleus, where it affects gene transcription, and roles outside the nucleus, where it regulates unknown effectors. To determine which pool of Wld S accounts for its axon-protective effects, we developed a strategy to control the spatial expression of proteins within neurons. This strategy couples a chemical genetic method to control protein stability with microfluidic culturing. Using neurons that are selectively deficient in Wld S in axons, we show that the axonal pool of Wld S is necessary for protection from axon degeneration. These results implicate an axonal pathway regulated by Wld S that controls axon degeneration.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalChemistry and Biology
Volume19
Issue number2
DOIs
StatePublished - Feb 24 2012

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Neurons
Axons
Proteins
Wallerian Degeneration
Microfluidics
Protein Stability
Protein S
Pathologic Processes
Transcription
Nervous System Diseases
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Chemical genetic-mediated spatial regulation of protein expression in neurons reveals an axonal function for wld S . / Cohen, Michael S.; Ghosh, Ananda K.; Kim, Hyung Joon; Jeon, Noo Li; Jaffrey, Samie R.

In: Chemistry and Biology, Vol. 19, No. 2, 24.02.2012, p. 179-187.

Research output: Contribution to journalArticle

Cohen, Michael S. ; Ghosh, Ananda K. ; Kim, Hyung Joon ; Jeon, Noo Li ; Jaffrey, Samie R. / Chemical genetic-mediated spatial regulation of protein expression in neurons reveals an axonal function for wld S In: Chemistry and Biology. 2012 ; Vol. 19, No. 2. pp. 179-187.
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