Actin filaments and microtubule dual-granule transport in human adhered platelets: the role of alpha-dystrobrevins.
Upon activation with physiological stimuli, human platelets undergo morphological changes, centralizing their organelles and secreting effector molecules at the site of vascular injury. Previous studies have indicated that the actin filaments and microtubules of suspension-activated platelets play a critical role in granule movement and exocytosis; however, the participation of these cytoskeleton elements in adhered platelets remains unexplored. alpha- and beta-dystrobrevin members of the dystrophin-associated protein complex in muscle and non-muscle cells have been described as motor protein receptors that might participate in the transport of cellular components in neurons. Recently, we characterized the expression of dystrobrevins in platelets; however, their functional diversity within this cellular model had not been elucidated. The present study examined the contribution of actin filaments and microtubules in granule trafficking during the platelet adhesion process using cytoskeleton-disrupting drugs, quantification of soluble P-selectin, fluorescence resonance transfer energy analysis and immunoprecipitation assays. Likewise, we assessed the interaction of alpha-dystrobrevins with the ubiquitous kinesin heavy chain. Our results strongly suggest that microtubules and actin filaments participate in the transport of alpha and dense granules in the platelet adhesion process, during which alpha-dystrobrevins play the role of regulatory and adaptor proteins that govern trafficking events.
Instituto Politécnico Nacional, México DF, Mexico. dcereced@prodigy.net.mx <dcereced@prodigy.net.mx>
Doris
D
Cerecedo
Bulmaro
B
Cisneros
Ricardo
R
Mondragón
Sirenia
S
González
Iván J
IJ
Galván
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D001792:Blood Platelets / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D049029:Dystrophin-Associated Proteins / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D010973:Platelet Adhesiveness / Q000502:physiology*; D014404:Tubulin / Q000502:physiology
D000199:Actins; D049029:Dystrophin-Associated Proteins; D014404:Tubulin; C098885:dystrobrevin