STUDY OF MYELIN ENZYMES &RECEPTORS &THE AXON

Project Details

Description

Since discovery of a muscarinic receptor in myelin we have
broadened this grant (reflected in title) to include the study of
both receptors and enzymes which are intrinsic to the myelin
membrane. Current work indicating that this receptor is linked to
phosphoinositide metabolism will be continued to determine the
details of phosphoinositide breakdown and resynthesis within
myelin, as elicited by muscarinic agonists as well as depolarizing
agents. A key enzyme in this process, phosphoinositide-specific
phospholipase C, will be isolated from myelin and its properties
studied. This will also be done with phosphatidylinositol
synthetase, an enzyme presumed to be present in myelin because
of its role in resynthesis of phosphoinositides. A third protein to
be isolated from myelin is the GTP-binding protein which
mediates the receptor-lined hydrolysis of phosphoinositides.
Possible involvement of the axon in supplying subtrates for these
reactions (as previously demonstrated for other myelin lipids) will
be investigated by use of the optic system/axonal transport
paradigm. Other substrates to be similarly studied are those
required for sphingolipid synthesis, e.g. cerebrosides (enzymes
involved in synthesis of the latter have been localized in myelin).
These investigations will further establish the nature of the
metabolic linkage between the axon and its myelin sheath. New
myelin enzymes to be sought include those involved in sphingolipid
synthesis, principally the lipophilic moieties. Since receptor-
mediated breakdown of phosphoinositides leads to formation of
diacylglycerol, an activator of protein kinase C, we shall attempt
to identify myelin proteins (e.g. basic protein) whose
phosphorylation is significantly affected by muscarinic agonists.
Finally, we shall attempt to further characterize the adenylate
cyclase-system which we recently discovered to be present in
myelin.
StatusFinished
Effective start/end date12/31/895/31/99

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

ASJC

  • Medicine(all)
  • Neuroscience(all)
  • Atomic and Molecular Physics, and Optics
  • Biochemistry
  • Cell Biology

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