Prominin-1 (CD133) modulates the architecture and dynamics of microvilli

被引：32

作者：

Thamm, Kristina ^{[1
,2
]}

Simaite, Deimante ^{[1
,2
,5
]}

Karbanova, Jana ^{[1
,2
]}

Bermudez, Vicente ^{[1
,2
,6
]}

Reichert, Doreen ^{[1
,2
,7
]}

Morgenstern, Anne ^{[1
,2
]}

Bornhaeuser, Martin ^{[3
]}

Huttner, Wieland B. ^{[4
]}

Wilsch-Braeuninger, Michaela ^{[4
]}

Corbeil, Denis ^{[1
,2
]}

机构：

[1] Tech Univ Dresden, Ctr Biotechnol, Tissue Engn Labs, Tatzberg 47-49, D-01307 Dresden, Germany

[2] Tech Univ Dresden, Ctr Mol & Cellular Bioengn, Dresden, Germany

[3] Univ Hosp Carl Gustav Carus, Med Clin & Polyclin 1, Dresden, Germany

[4] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany

[5] Sanofi Aventis Deutschland GmbH, Ind Pk Hoechst, Frankfurt, Germany

[6] Inst Invest Bioquim Bahia Blanca, B8000FWB, Bahia Blanca, Buenos Aires, Argentina

[7] Heinrich Heine Univ, Clin Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany

来源：

TRAFFIC | 2019年 / 20卷 / 01期

关键词：

Arp2/3; complex; CD133; epithelial cells; membrane vesicles; microvilli; phosphoinositide; 3-kinase; prominin-1; CELL MARKER CD133; POLYTOPIC MEMBRANE-PROTEIN; HEMATOPOIETIC STEM; ARP2/3; COMPLEX; EPITHELIAL-CELLS; BRUSH-BORDER; PLASMALEMMAL PROTRUSIONS; NEURAL PROGENITORS; LIPID MICRODOMAINS; ACTIN-FILAMENTS;

D O I：

10.1111/tra.12618

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：39 / 60

页数：22

共 104 条

[1] CD133 is a modifier of hematopoietic progenitor frequencies but is dispensable for the maintenance of mouse hematopoietic stem cells [J].