Munc18 interacting proteins: ADP-ribosylation factor-dependent coat proteins that regulate the traffic of beta-Alzheimer's precursor protein.
Coat proteins cycle between soluble and membrane-bound locations at the time of vesicle biogenesis and act to regulate the assembly of the vesicle coat that determines the specificity in cargo selection and the destination of the vesicle. A transmembrane cargo protein, an Arf GTPase, and a coat protein (e.g. COPs, APs, or GGAs) are minimal components required for budding of vesicles. Munc18 interacting proteins (MINTs) are a family of three proteins implicated in the localization of receptors to the plasma membrane. We show that MINTs bind Arfs directly, co-localize with Arf and the Alzheimer's precursor protein (beta-APP) to regions of the Golgi/trans-Golgi network, and can co-immunoprecipitate clathrin. We demonstrate that MINTs bind Arfs through a region of the PTB domain and the PDZ2 domain, and Arf-MINT interaction is necessary for the increased cellular levels of beta-APP produced by MINT overexpression. Knockdown (small interference RNA) experiments implicate beta-APP as a transmembrane cargo protein that works together with MINTs. We propose that MINTs are a family of Arf-dependent, vesicle-coat proteins that can regulate the traffic of beta-APP.
Hill
Karen
K
Department of Biochemistry, School of Medicine, Emory University, Atlanta, Georgia 30322-3050, USA.
Li
Yawei
Y
Bennett
Matt
M
McKay
Melissa
M
Zhu
Xinjun
X
Shern
Jack
J
Torre
Enrique
E
Lah
James J
JJ
Levey
Allan I
AI
Kahn
Richard A
RA
D020727:ADP-Ribosylation Factors / Q000737:chemistry / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D015820:Cadherins; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D051938:Munc18 Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*
C491636:APBA2 protein, human; C117536:APBA3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C485532:Apba3 protein, rat; D015820:Cadherins; D002352:Carrier Proteins; D002966:Clathrin; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D020126:Brefeldin A; C116687:ARF3 protein, human; C492129:Arf3 protein, rat; D020727:ADP-Ribosylation Factors