Project: Research project

Project Details


Neurons synthesize, sort, and transport numerous membrane
proteins for localization to highly specialized functional domains
on their plasma membranes. The molecular mechanisms whereby
they accomplish this targeting are unknown. The long range goal
of this project is to determine the molecular signal(s) responsible
for targeting neuronal membrane proteins to their appropriate
destinations on the cell surface and the mechanism whereby they
are retained within selected regions of the plasma membrane. As
a first step in understanding these mechanisms we have chosen to
study the processing, transport, and localization of
acetylocholinesterase (AChE) in tissue-cultured CNS neurons.
AChE is the enzyme that hydrolyses the acetylcholine released by
cholinergic nerves. This enzyme exists as a complex family of
oligomeric forms, a subset of which are rapidly transported down
the axon. In addition, a single integral membrane form of AChE
is targeted to the surface plasma membrane in tissue cultured
neurons where it is localized in clusters along the neurites. It is
likely that the mechanism(s) employed by neurons to sort and
transport AChE molecules will be shared by most if not all rapidly
transported neuronal membrane proteins, whereas the final
targeting will depend upon specific characteristics of subsets of
membrane proteins. These are basic studies that will lead to an
understanding of how all nerve cells sort and transport membrane
proteins to specific regions of their plasma membranes. Our specific aims during the tenure of this proposal are: 1) to
determine where, when, and how the signal specifying membrane
localization of AChE in CNS neurons occurs; 2) to clone and
identify full length cDNAs encoding the AChE polypeptides from
chicken CNS neurons using a full length Torpedo AChE cDNA as a
probe, 3) to express these cDNAs in mouse L cells to study the
fate of the chicken AChE polypeptides, and 4) to inject in vitro
synthesized AChE, VSV G-glycoprotein, and IL2 receptor mRNA
into identified neurons of the leech (Hirudo medicinalis) to study
the transport and localization of an identified rapidly transported
protein and foreign membrane proteins in vivo.
Effective start/end date6/1/885/31/93


  • National Institutes of Health
  • National Institutes of Health: $69,390.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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