Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin

Kristin Walther; M Kasim Diril; Nadja Jung; Volker Haucke

doi:10.1073/pnas.0307862100

Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin

Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):964-9. doi: 10.1073/pnas.0307862100. Epub 2004 Jan 15.

Authors

Kristin Walther¹, M Kasim Diril, Nadja Jung, Volker Haucke

Affiliation

¹ Department of Biochemistry II, Zentrum für Biochemie and Molekulare Zellbiologie, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.

Abstract

Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis. This process involves the coordinated assembly of clathrin and adaptor proteins and the concomitant selection of cargo proteins. Here, we demonstrate that the endocytotic protein stonin 2 localizes to axonal vesicle clusters through its micro-homology domain. Interaction of this domain with synaptotagmin I is sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable of binding to the alpha-adaptin ear domain and to micro2. Mutation of the tyrosine motif-binding pocket of micro2 abolishes recognition of the WVxF peptide, suggesting that association with stonin 2 renders AP-2 incompetent to sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Protein Complex 2 / metabolism*
Adaptor Protein Complex alpha Subunits / metabolism
Adaptor Proteins, Vesicular Transport
Amino Acid Sequence
Animals
Brain / metabolism
Calcium-Binding Proteins*
Carrier Proteins / chemistry
Carrier Proteins / metabolism*
Cell Line
Endocytosis
Humans
Membrane Glycoproteins / metabolism*
Membrane Proteins / chemistry
Membrane Proteins / metabolism*
Molecular Sequence Data
Mutagenesis, Site-Directed
Nerve Tissue Proteins / metabolism*
Protein Binding
Synaptotagmin I
Synaptotagmins
Transferrin / metabolism
Vesicular Transport Proteins*

Substances

Adaptor Protein Complex 2
Adaptor Protein Complex alpha Subunits
Adaptor Proteins, Vesicular Transport
Calcium-Binding Proteins
Carrier Proteins
Membrane Glycoproteins
Membrane Proteins
Nerve Tissue Proteins
STON2 protein, human
SYT1 protein, human
Synaptotagmin I
Transferrin
Vesicular Transport Proteins
Synaptotagmins

Associated data

GENBANK/AK014958
GENBANK/AK036612