BECAS
BERMUDEZ vicente
artículos
Título:
Prominin-1 (CD133) modulates the architecture and dynamics of microvilli
Autor/es:
THAMM, KRISTINA; SIMAIT?, DEIMANT?; KARBANOVÁ, JANA; BERMÚDEZ, VICENTE; REICHERT, DOREEN; MORGENSTERN, ANNE; BORNHÄUSER, MARTIN; HUTTNER, WIELAND B.; WILSCH-BRÄUNINGER, MICHAELA; CORBEIL, DENIS
Revista:
TRAFFIC
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2019 vol. 20 p. 39 - 60
ISSN:
1398-9219
Resumen:
Prominin-1 is a cell surface biomarker that allows the identification of stem and cancer stem cells from different organs. It is also expressed in several differentiated epithelial and non-epithelial cells. Irrespective of the cell type, prominin-1 is associated with plasma membrane protrusions. Here, we investigate its impact on the architecture of membrane protrusions using microvilli of Madin-Darby canine kidney cells as the main model. Our high-resolution analysis revealed that upon the overexpression of prominin-1 the number of microvilli and clusters of them increased. Microvilli with branched and/or knob-like morphologies were observed and stimulated by mutations in the ganglioside-binding site of prominin-1. The altered phenotypes were caused by the interaction of prominin-1 with phosphoinositide 3-kinase and Arp2/3 complex. Mutation of tyrosine 828 of prominin-1 impaired its phosphorylation and thereby inhibited the aforementioned interactions abolishing altered microvilli. This suggests that the interplay of prominin-1-ganglioside membrane complexes, phosphoinositide 3-kinase and cytoskeleton components regulates microvillar architecture. Lastly, the expression of prominin-1 and its mutants modified the structure of filopodia emerging from fibroblast-like cells and silencing human prominin-1 in primary hematopoietic stem cells resulted in the loss of uropod-associated microvilli. Altogether, these findings strengthen the role of prominin-1 as an organizer of cellular protrusions.