Alternative titles; symbols
HGNC Approved Gene Symbol: CLASP2
Cytogenetic location: 3p22.3 Genomic coordinates (GRCh38) : 3:33,496,245-33,718,254 (from NCBI)
CLASP2 belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and regulate microtubule dynamics. CLASP2 functions in various microtubule-dependent processes, including cell division, cytoskeletal remodeling for cell migration, and vesicle transport between intracellular structures and the plasma membrane (summary by Langlais et al., 2012).
CLIP170 (179838) and CLIP115 (603432) are cytoplasmic linker proteins that associate specifically with the ends of growing microtubules and may act as anticatastrophe factors. Using a yeast 2-hybrid screen with an N-terminal region of CLIP115 as bait, followed by cDNA library screening, RACE analysis, and EST database searching, Akhmanova et al. (2001) identified mouse and human cDNAs encoding 2 CLIP-associated proteins, CLASP1 (605852) and CLASP2. The CLASPs are homologous to a Drosophila microtubule-associated protein termed Orbit or Mast. CLASP1 is identical to the protein encoded by a partial cDNA, KIAA0622, identified by Ishikawa et al. (1998), although the KIAA0622 protein lacks the N-terminal 249 amino acids of the 1,538-amino acid CLASP1 protein reported by Akhmanova et al. (2001). CLASP2 shares approximately 75% identity with the KIAA0627 protein, which is encoded by a partial cDNA also identified by Ishikawa et al. (1998). There are several CLASP isoforms due to alternative splicing. Northern blot analysis of mouse tissues detected highest expression of Clasp1 in brain, heart, and testis, while Clasp2 mRNAs were enriched in the brain. The Clasp2-beta transcript appeared to be brain-specific. By RT-PCR analysis, Ishikawa et al. (1998) detected variable but ubiquitous expression of CLASP2, or KIAA0627, except in spleen.
Akhmanova et al. (2001) showed that CLASPs bind CLIPs and microtubules, colocalize with the CLIPs at microtubule distal ends, and have microtubule-stabilizing effects in transfected cells. After serum induction, CLASPs relocalize to distal segments of microtubules at the leading edge of motile fibroblasts. Akhmanova et al. (2001) provided evidence that this asymmetric CLASP distribution is mediated by phosphatidylinositol 3-kinase (see 171834) and glycogen synthase kinase 3-beta (605004). Antibody injections suggested that CLASP2 is required for the orientation of stabilized microtubules toward the leading edge. The authors proposed that CLASPs are involved in the local regulation of microtubule dynamics in response to positional cues.
Using rat L6 myoblasts and mouse 3T3-L1 adipocytes, Langlais et al. (2012) determined that Clasp2 has a role in insulin (176730) signaling and glucose uptake. Confocal imaging of L6 myotubes revealed that Clasp2 colocalized with the glucose transporter Glut4 (SLC2A4; 138190) at the plasma membrane within areas of insulin-mediated cortical actin remodeling. Clasp2 underwent insulin-stimulated phosphorylation, and knockdown of Clasp2 via small interfering RNA inhibited insulin-stimulated Glut4 translocation along microtubules toward the plasma membrane. Knockdown of Clasp2 in adipocytes inhibited insulin-stimulated glucose transport. Langlais et al. (2012) concluded that CLASP2 has a role in insulin signaling and directs the delivery of GLUT4 to the plasma membrane for glucose uptake.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the CLASP2 gene, which they called KIAA0627, to chromosome 3.
Hartz (2013) mapped the CLASP2 gene to chromosome 3p22.3 based on an alignment of the CLASP2 sequence (GenBank AB014527) with the genomic sequence (GRCh37).
Akhmanova, A., Hoogenraad, C. C., Drabek, K., Stepanova, T., Dortland, B., Verkerk, T., Vermeulen, W., Burgering, B. M., De Zeeuw, C. I., Grosveld, F., Galjart, N. CLASPs are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell 104: 923-935, 2001. [PubMed: 11290329] [Full Text: https://doi.org/10.1016/s0092-8674(01)00288-4]
Hartz, P. A. Personal Communication. Baltimore, Md. 11/1/2013.
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 169-176, 1998. [PubMed: 9734811] [Full Text: https://doi.org/10.1093/dnares/5.3.169]
Langlais, P., Dillon, J. L., Mengos, A., Baluch, D. P., Ardebili, R., Miranda, D. N., Xie, X., Heckmann, B. L., Liu, J., Mandarino, L. J. Identification of a role for CLASP2 in insulin action. J. Biol. Chem. 287: 39245-39253, 2012. [PubMed: 22992739] [Full Text: https://doi.org/10.1074/jbc.M112.394148]