Identification of Hic-5 as a novel regulatory factor for integrin αIIbβ3 activation and platelet aggregation in mice.
BACKGROUND
Integrin αIIbβ3 plays key roles in platelet aggregation and subsequent thrombus formation. Hydrogen peroxide-inducible clone-5 (Hic-5), a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbβ3 at its cytoplasmic strand.


OBJECTIVE
Hic-5 function in αIIbβ3 activation and subsequent platelet aggregation remains unknown. To address this question, platelets from Hic-5(-/-) mice were analyzed.


RESULTS
Hic-5(-/-) mice displayed a significant hemostatic defect and resistance to thromboembolism, which were explained in part by weaker thrombin-induced aggregation in Hic-5(-/-) platelets. Mechanistically, Hic-5(-/-) platelets showed limited activation of αIIbβ3 upon thrombin treatment. Morphological alteration in Hic-5(-/-) platelets after thrombin stimulation on fibrinogen plates was also limited. As a direct consequence, the quantity of actin co-immunoprecipitating with the activated αIIbβ3 was smaller in Hic-5(-/-) platelets than in wild-type platelets.


CONCLUSIONS
We identified Hic-5 as a novel and specific regulatory factor for thrombin-induced αIIbβ3 activation and subsequent platelet aggregation in mice.
Department of Biochemistry, Showa University School of Medicine, Tokyo Department of Clinical Toxicology, Showa University School of Pharmacy, Tokyo, Japan. shuri@pharm.showa-u.ac.jp
J R
JR
Kim-Kaneyama
A
A
Miyauchi
X F
XF
Lei
S
S
Arita
T
T
Mino
N
N
Takeda
K
K
Kou
K
K
Eto
T
T
Yoshida
T
T
Miyazaki
S
S
Shioda
A
A
Miyazaki
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D060588:LIM Domain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D010974:Platelet Aggregation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C090090:Tgfb1i1 protein, mouse