Cordon bleu promotes the assembly of brush border microvilli.
Microvilli are actin-based protrusions found on the surface of diverse cell types, where they amplify membrane area and mediate interactions with the external environment. In the intestinal tract, these protrusions play central roles in nutrient absorption and host defense and are therefore essential for maintaining homeostasis. However, the mechanisms controlling microvillar assembly remain poorly understood. Here we report that the multifunctional actin regulator cordon bleu (COBL) promotes the growth of brush border (BB) microvilli. COBL localizes to the base of BB microvilli via a mechanism that requires its proline-rich N-terminus. Knockdown and overexpression studies show that COBL is needed for BB assembly and sufficient to induce microvillar growth using a mechanism that requires functional WH2 domains. We also find that COBL acts downstream of the F-BAR protein syndapin-2, which drives COBL targeting to the apical domain. These results provide insight into a mechanism that regulates microvillar growth during epithelial differentiation and have significant implications for understanding the maintenance of intestinal homeostasis.
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240.
Nathan E
NE
Grega-Larson
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240.
Scott W
SW
Crawley
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240.
Amanda L
AL
Erwin
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240 matthew.tyska@vanderbilt.edu.
Matthew J
MJ
Tyska
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D053669:Syndecan-2 / Q000378:metabolism
D000199:Actins; C561633:Cobl protein, human; D008840:Microfilament Proteins; D053669:Syndecan-2