QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 4, 1415-1426, April 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-12-1239v1 19/4/1415    most recent Alert me when this article is cited Alert me if a correction is posted Services Related articles in Mol. Biol. Cell Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Craige, B. Articles by Faundez, V. PubMed PubMed Citation Articles by Craige, B. Articles by Faundez, V.

Phosphatidylinositol-4-Kinase Type II Alpha Contains an AP-3–sorting Motif and a Kinase Domain That Are Both Required for Endosome Traffic

Branch Craige^*,, Gloria Salazar, and Victor Faundez^,

*Graduate Program in Biochemistry, Cell, and Developmental Biology, and Department of Cell Biology, and Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322

Submitted December 12, 2007; Revised January 9, 2008; Accepted January 25, 2008
Monitoring Editor: Sandra Lemmon

InCytes from MBC

The adaptor complex 3 (AP-3) targets membrane proteins from endosomes to lysosomes, lysosome-related organelles and synaptic vesicles. Phosphatidylinositol-4-kinase type II (PI4KII) is one of several proteins possessing catalytic domains that regulate AP-3–dependent sorting. Here we present evidence that PI4KII uniquely behaves both as a membrane protein cargo as well as an enzymatic regulator of adaptor function. In fact, AP-3 and PI4KII form a complex that requires a dileucine-sorting motif present in PI4KII. Mutagenesis of either the PI4KII-sorting motif or its kinase-active site indicates that both are necessary to interact with AP-3 and properly localize PI4KII to LAMP-1–positive endosomes. Similarly, both the kinase activity and the sorting signal present in PI4KII are necessary to rescue endosomal PI4KII siRNA-induced mutant phenotypes. We propose a mechanism whereby adaptors use canonical sorting motifs to selectively recruit a regulatory enzymatic activity to restricted membrane domains.

Address correspondence to: Victor Faundez (faundez{at}cellbio.emory.edu)

Related articles in Mol. Biol. Cell:

InCytes from MBC, April 2008

Mol. Biol. Cell 2008 19: 1281. [PDF]