Alternative titles; symbols
HGNC Approved Gene Symbol: CLASP1
Cytogenetic location: 2q14.2-q14.3 Genomic coordinates (GRCh38) : 2:121,337,776-121,649,462 (from NCBI)
CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003).
CLIP170 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 and CLASP2 (605853). 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 ubiquitous expression of CLASP1, which they called KIAA0622.
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.
Maiato et al. (2003) showed that CLASP1 localizes preferentially near the plus ends of growing spindle microtubules and is also a component of a kinetochore region they termed the outer corona. A truncated form of CLASP1 lacking the kinetochore-binding domain behaved as a dominant negative, leading to the formation of radial arrays of microtubule bundles that were highly resistant to depolymerization. Microinjection of CLASP1-specific antibodies suppressed microtubule dynamics at kinetochores and throughout the spindle, resulting in the formation of monopolar asters with chromosomes buried in the interior. Incubation with microtubule-stabilizing drugs rescued the kinetochore association with microtubule plus ends at the periphery of the asters. Maiato et al. (2003) concluded that CLASP1 is required at kinetochores for attached microtubules to exhibit normal dynamic behavior.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the CLASP1 gene, which they called KIAA0622, to chromosome 2.
Hartz (2013) mapped the CLASP1 gene to chromosome 2q14.2 based on an alignment of the CLASP1 sequence (GenBank AB014522) with the genomic sequence (GRCh37).
Lemos et al. (2000) stated that Mast, the Drosophila ortholog of CLASP1, localized to centrosomes, mitotic spindles, centromeres, and spindle midzones during mitosis. They found that Mast showed strong affinity for polymerized microtubules. Mutations in Mast caused larval or pupal lethality. Neuroblasts of homozygous or hemizygous larvae carrying Mast mutant alleles were highly polyploid and showed severe mitotic abnormalities, including formation of mono- and multipolar spindles that were organized by an irregular number of microtubule-organizing centers of abnormal size and shape.
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. 10/31/2013.
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]
Lemos, C. L., Sampaio, P., Maiato, H., Costa, M., Omel'yanchuk, L. V., Liberal, V., Sunkel, C. E. Mast, a conserved microtubule-associated protein required for bipolar mitotic spindle organization. EMBO J. 19: 3668-3682, 2000. [PubMed: 10899121] [Full Text: https://doi.org/10.1093/emboj/19.14.3668]
Maiato, H., Fairley, E. A. L., Rieder, C. L., Swedlow, J. R., Sunkel, C. E., Earnshaw, W. C. Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics. Cell 113: 891-904, 2003. [PubMed: 12837247] [Full Text: https://doi.org/10.1016/s0092-8674(03)00465-3]