A novel syntaxin 6-interacting protein, SHIP164, regulates syntaxin 6-dependent sorting from early endosomes.
Membrane fusion is dependent on the function of SNAREs and their alpha-helical SNARE motifs that form SNARE complexes. The Habc domains at the N-termini of some SNAREs can interact with their associated SNARE motif, Sec1/Munc18 (SM) proteins, tethering proteins or adaptor proteins, suggesting that they play an important regulatory function. We screened for proteins that interact with the Habc domain of Syntaxin 6, and isolated an uncharacterized 164-kDa protein that we named SHIP164. SHIP164 is part of a large (approximately 700 kDa) complex, and interacts with components of the Golgi-associated retrograde protein (GARP) tethering complex. Depletion of GARP subunits or overexpression of Syntaxin 6 results in a redistribution of soluble SHIP164 to endosomal structures. Co-overexpression of Syntaxin 6 and SHIP164 produced excessive tubulation of endosomes, and perturbed the transport of cation-independent mannose-6-phosphate receptor (CI-MPR) and transferrin receptor. Thus,we propose that SHIP164 functions in trafficking through the early/recycling endosomal system.
Otto
Grant P
GP
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, UK.
Razi
Minoo
M
Morvan
Jöelle
J
Stenner
Frank
F
Tooze
Sharon A
SA
D020816:Amino Acid Motifs / Q000235:genetics; D015703:Antigens, CD; D001692:Biological Transport / Q000235:genetics; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008360:Mannosephosphates; D008561:Membrane Fusion / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C068126:CD71 antigen; D008360:Mannosephosphates; D050765:Qa-SNARE Proteins; D017527:Receptor, IGF Type 2; D011990:Receptors, Transferrin; D050600:SNARE Proteins; C027693:mannose-6-phosphate