REGULATION OF ACETYLCHOLINESTERASE SYNTHESIS/ASSEMBLY

Project: Research project

Description

The importance of acetylcholinesterase (AChE) lies in its physiological
role in neurotransmission, its prominence as a marker for nerve-muscle
interactions, and because it is a complex family of oligomeric forms with
multiple subcellular locations. Studies of this enzyme will detail how
muscle cells regulate the synthesis and assembly of synaptic components in
particular, and in broader terms, will provide specific information
concerning the mechanisms of regulation and localization of membrane and
secreted proteins. The goal of this proposal is to determine the molecular
and cellular mechanisms regulating synthesis, assembly, degradation, and
localization of the multiple oligomeric forms of AChE in muscle. The
overall objective is to determine the relative contributions of the many
post-translational events in regulating AChE localization and metabolism. The specific aims are to: 1) determine whether differences in primary
structure alone account for the different oligomeric forms and subcellular
localizations of AChE; these studies entail isolating isotopically labeled
AChE polypeptides from different subcellular compartments and comparing
their primary sequences by peptide mapping; 2) determine the structural
differences between active and inactive AChE molecules and the cellular
mechanisms involved in sorting the two classes; these studies employ a
variety of pulse/chase paradigms in conjunction with other biochemical
methods to identify modifications, and to determine when and where in the
cell these modifications occur; 3) identify the subcellular location of the
several AChE forms by indirect immunofluorescence and electron microscopy
following differential extractions and enzymatic treatments; 4) study the
specific mechanisms of intracellular degradation, assembly, and processing
of the AChE polypeptide chains in order to 5) study the role of muscle
activity in regulating the synthesis, activation, assembly, transport, and
ultimately localization of the multiple AChE forms.
StatusFinished
Effective start/end date5/1/853/31/11

Funding

  • National Institutes of Health
  • National Institutes of Health: $286,825.00
  • National Institutes of Health: $292,679.00
  • National Institutes of Health: $334,188.00
  • National Institutes of Health
  • National Institutes of Health: $308,675.00
  • National Institutes of Health
  • National Institutes of Health: $89,063.00
  • National Institutes of Health
  • National Institutes of Health: $310,403.00
  • National Institutes of Health
  • National Institutes of Health: $240,334.00
  • National Institutes of Health: $301,362.00
  • National Institutes of Health: $258,486.00
  • National Institutes of Health
  • National Institutes of Health: $301,420.00
  • National Institutes of Health
  • National Institutes of Health: $94,391.00
  • National Institutes of Health: $268,827.00
  • National Institutes of Health
  • National Institutes of Health: $75,750.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $22,964.00
  • National Institutes of Health: $319,715.00
  • National Institutes of Health
  • National Institutes of Health: $296,819.00
  • National Institutes of Health: $8,115.00
  • National Institutes of Health: $286,825.00

Fingerprint

Acetylcholinesterase
Synapses
Muscles
Muscle Cells
Second Messenger Systems
Skeletal Muscle Fibers

ASJC

  • Medicine(all)