High impact information on TRAK2

• Identification of {gamma}-Aminobutyric Acid Receptor-interacting Factor 1 (TRAK2) as a Trafficking Factor for the K+ Channel Kir2.1 [1].
• Co-immunoprecipitation and confocal imaging strategies further showed that GRIF-1 can bind to the tetrameric kinesin light-chain/kinesin heavy-chain complex [2].
• The GRIF-1 binding site of KIF5C was mapped using truncation constructs in yeast two-hybrid interaction assays, co-immunoprecipitations, and co-localization studies following expression in mammalian cells [2].
• One of these clones was identical to the protein of unknown function isolated previously as gamma-aminobutyric acid receptor-interacting factor 1 (GRIF-1) (Beck, M., Brickley, K., Wilkinson, H., Sharma, S., Smith, M., Chazot, P., Pollard, S., and Stephenson, F. (2002) J. Biol. Chem. 277, 30079-30090) [1].
• Quantitative microscopy and flow cytometry analysis of immunolabeled surface Kir2.1 channel showed that GRIF-1 significantly increased the number of Kir2.1 channels in the plasma membrane of COS and HEK293 cells [1].

Anatomical context of TRAK2

• These findings support a role for GRIF-1 as a kinesin adaptor molecule requisite for the anterograde delivery of defined cargoes such as mitochondria and/or vesicles incorporating beta2 subunit-containing GABA(A) receptors, in the brain [2].
• Like Hrs, both overexpression and siRNA-mediated depletion of GRIF1 inhibit the degradation of internalized epidermal growth factor receptors and block the trafficking of the receptors from early endosomes to the lysosomal pathway [3].
• GRIF-1 [GABA(A) (gamma-aminobutyric acid(A)) receptor interacting factor-1] is a member of a coiled-coil family of proteins thought to function as adaptors in the anterograde trafficking of organelles utilizing the kinesin-1 motor proteins to synapses [4].

Associations of TRAK2 with chemical compounds

• gamma-Aminobutyric acid, type A (GABA(A)) receptor interacting factor-1 (GRIF-1) and N-acetylglucosamine transferase interacting protein (OIP) 106 are both members of a newly identified coiled-coil family of proteins [2].

Physical interactions of TRAK2

• Yeast two-hybrid screen and co-immunoprecipitation analysis reveal that GRIF1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting machinery [3].

Other interactions of TRAK2

• Refined studies using yeast two-hybrid interactions and co-immunoprecipitations showed that GRIF-1 and GRIF-1-(124-283) associated with the cargo binding region within the KIF5C non-motor domain [2].

Analytical, diagnostic and therapeutic context of TRAK2

• Yeast two-hybrid assays showed that an N-terminal region of GRIF-1 interacts with a C-terminal region of Kir2 [1].

References