The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Drabek, K (Author) Other; Gutierrez, L (Author) Other; Vermeij, M (Author) Other; Clapes, T (Author) Other; Patel, SR (Author) Other; Boisset, JC (Author) Other; van Haren, J (Author) Other; Pereira, AL (Author) Other; Liu, Z (Author) Other; Akinci, U (Author) Other; Nikolic, T (Author) Other; van IJcken, W (Author) Other; van den Hout, M (Author) Other; Meinders, M (Author) Other; Melo, C (Author) Other; Sambade, C (Author) Other; Drabek, D (Author) Other; Hendriks, RW (Author) Other; Philipsen, S (Author) Other; Mommaas, M (Author) Other; Grosveld, F (Author) Other; Helder Maiato (Author) FMUP; Italiano, JE (Author) Other; Robin, C (Author) Other; Galjart, N (Author) Other

Journal

Title: Cell Reports

Vol. 2

Pages: 781-788

ISSN: 2211-1247

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 12 Citations

Other information

Authenticus ID: P-002-4HP

DOI: 10.1016/j.celrep.012.08.040

Abstract (EN): Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects in megakaryopoiesis, in erythropoiesis, and in the maintenance of hematopoietic stem cell activity. Furthermore, microtubule stability and organization are affected upon attachment of Clasp2 knockout hematopoietic stem-cell-enriched populations, and these cells do not home efficiently toward their bone marrow niche. Strikingly, CLASP2-deficient hematopoietic stem cells contain severely reduced mRNA levels of c-Mpl, which encodes the thrombopoietin receptor, an essential factor for megakaryopoiesis and hematopoietic stem cell maintenance. Our data suggest that thrombopoietin signaling is impaired in Clasp2 knockout mice. We propose that the CLASP2-mediated stabilization of microtubules is required for proper attachment, homing, and maintenance of hematopoietic stem cells and that this is necessary to sustain c-Mpl transcription.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8