Abstract
Secretory carrier membrane proteins (SCAMPs) are ubiquitous components of recycling vesicles that shuttle between the plasma membrane, endosomes, and the trans-Golgi complex. SCAMPs contain multiple N-terminal NPF repeats and four highly conserved transmembrane regions. NPF repeats often interact with EH domain proteins that function in budding of transport vesicles from the plasma membrane or the Golgi complex. We now show that the NPF repeats of SCAMP1 bind to two EH domain proteins, intersectin 1, which is involved in endocytic budding at the plasma membrane, and gamma-synergin, which may mediate the budding of vesicles in the trans-Golgi complex. Expression of SCAMP1 lacking the N-terminal NPF repeats potently inhibited transferrin uptake by endocytosis. Our data suggest that one of the functions of SCAMPs is to participate in endocytosis via a mechanism which may involve the recruitment of clathrin coats to the plasma membrane and the trans-Golgi network.
Highlights
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF242544
We have pursued the hypothesis that SCAMPs are intrinsic membrane proteins of recycling vesicles which serve as assembly sites for clathrin coats on the plasma membrane and Golgi apparatus
The presence of NPF repeats in SCAMPs was intriguing because NPF repeats represent binding sites for EH domains, autonomously folding protein modules that are primarily observed in proteins involved in endocytosis [8, 9]
Summary
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF242544 (for full-length rat synergin sequence). The presence of NPF repeats in the N terminus of SCAMPs suggests a potential role in binding to cytosolic EH domain proteins, possibly during endocytosis. It seems likely that specific binding sites for the adaptor protein complex AP-2 nucleate assembly of the clathrin coat on the plasma membrane (20 –22). Of clathrin coats on intracellular membranes, e.g. the trans-Golgi apparatus, likely involve recruitment of the appropriate adaptor complexes, such as AP-1, to the site of budding [23]. Synaptotagmins are primarily expressed in neurons, with extremely low levels of some isoforms outside of the brain This makes it unlikely that synaptotagmins represent universal AP-2 assembly sites that are present in all eukaryotic cells. We have pursued the hypothesis that SCAMPs are intrinsic membrane proteins of recycling vesicles which serve as assembly sites for clathrin coats on the plasma membrane and Golgi apparatus
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