Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

A peptide zipcode sufficient for anterograde transport within amyloid precursor protein.

Satpute-Krishnan P., DeGiorgis J.A., Conley M.P., Jang M., Bearer E.L.

Fast anterograde transport of membrane-bound organelles delivers molecules synthesized in the neuronal cell body outward to distant synapses. Identification of the molecular "zipcodes" on organelles that mediate attachment and activation of microtubule-based motors for this directed transport is a major area of inquiry. Here we identify a short peptide sequence (15 aa) from the cytoplasmic C terminus of amyloid precursor protein (APP-C) sufficient to mediate the anterograde transport of peptide-conjugated beads in the squid giant axon. APP-C beads travel at fast axonal transport rates (0.53 mum/s average velocity, 0.9 mum/s maximal velocity) whereas beads coupled to other peptides coinjected into the same axon remain stationary at the injection site. This transport appears physiologic, because it mimics behavior of endogenous squid organelles and of beads conjugated to C99, a polypeptide containing the full-length cytoplasmic domain of amyloid precursor protein (APP). Beads conjugated to APP lacking the APP-C domain are not transported. Coinjection of APP-C peptide reduces C99 bead motility by 75% and abolishes APP-C bead motility, suggesting that the soluble peptide competes with protein-conjugated beads for axoplasmic motor(s). The APP-C domain is conserved (13/15 aa) from squid to human, and peptides from either squid or human APP behave similarly. Thus, we have identified a conserved peptide zipcode sufficient to direct anterograde transport of exogenous cargo and suggest that one of APP's roles may be to recruit and activate axonal machinery for endogenous cargo transport.

Proc. Natl. Acad. Sci. U.S.A. 103:16532-16537(2006) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again