The microtubule plus-end tracking protein CLASP2 is required for hematopoiesis and hematopoietic stem cell maintenance.
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.
Department of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Ksenija
K
Drabek
Laura
L
Gutiérrez
Marcel
M
Vermeij
Thomas
T
Clapes
Sunita R
SR
Patel
Jean-Charles
JC
Boisset
Jeffrey
J
van Haren
Ana L
AL
Pereira
Zhe
Z
Liu
Umut
U
Akinci
Tatjana
T
Nikolic
Wilfred
W
van Ijcken
Mirjam
M
van den Hout
Marjolein
M
Meinders
Clara
C
Melo
Clara
C
Sambade
Dubravka
D
Drabek
Rudi W
RW
Hendriks
Sjaak
S
Philipsen
Mieke
M
Mommaas
Frank
F
Grosveld
Helder
H
Maiato
Joseph E
JE
Italiano
Catherine
C
Robin
Niels
N
Galjart
D000818:Animals; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D015398:Signal Transduction; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism
C506523:CLASP2 protein, mouse; D008869:Microtubule-Associated Proteins; D013926:Thrombopoietin