title: Interaction of Grb2 SH3 domain with UVRAG in an Alzheimer's disease-like scenario.
abstract: Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein which participates in trafficking pathways alongside its role in signaling. Proteins important for actin remodeling and cellular compartmentalization contain SRC Homology 3 (SH3) binding motifs that interact with Grb2. While studying the Grb2-amyloid precursor protein (APP) intracellular domain (AICD) interaction in Alzheimer's disease cell line models, it was seen that Grb2 colocalized to compartments that mature into autophagosomes. The entrapping of AICD in the Grb2 vesicles and its clearance via autophagosomes was a survival contrivance on the part of the cell. Here, we report that Grb2, when in excess, interacts with ultraviolet radiation resistance-associated gene protein (UVRAG) under excess conditions of AICD-Grb2 or Grb2. The N-terminal SH3 domain of Grb2 specifically interacts with UVRAG, unlike the C-terminal SH3 domain. This interaction helps to understand the role of Grb2 in the autophagic maturation of vesicles.
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064, India.
authors.forename: Kasturi
authors.initials: K
authors.lastname: Roy
authors.forename: Oishee
authors.initials: O
authors.lastname: Chakrabarti
authors.forename: Debashis
authors.initials: D
authors.lastname: Mukhopadhyay
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D025521:Tumor Suppressor Proteins; C408122:UVRAG protein, human
keywords: Beclin 1; Beclin1; Grb2; UVRAG; autophagie; autophagy; endophilin B1; endophilline B1