PT  - JOURNAL ARTICLE
AU  - Christian Hartmann
AU  - Eva-Maria Thüring
AU  - Birgitta E. Michels
AU  - Denise Pajonczyk
AU  - Sophia Leußink
AU  - Lilo Greune
AU  - Frauke Brinkmann
AU  - Mark Glaesner-Ebnet
AU  - Eva Wardelmann
AU  - Thomas Zobel
AU  - M. Alexander Schmidt
AU  - Volker Gerke
AU  - Klaus Ebnet
TI  - A novel adhesive complex at the base of intestinal microvilli
AID  - 10.1101/2021.01.25.428038
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.25.428038
4099  - http://biorxiv.org/content/early/2021/02/04/2021.01.25.428038.short
4100  - http://biorxiv.org/content/early/2021/02/04/2021.01.25.428038.full
AB  - Intestinal epithelial cells form dense arrays of microvilli at the apical membrane to enhance their functional capacity. Microvilli contain a protocadherin-based intermicrovillar adhesion complex localized at their tips which regulates microvillar length and packaging. Here, we identify a second adhesive complex in microvilli of intestinal epithelial cells. This complex is localized at the basal region of microvilli and consists of the adhesion molecule TMIGD1, the phosphoprotein EBP50 and the F-actin – plasma membrane cross-linking protein ezrin. Ternary complex formation requires unmasking of the EBP50 PDZ domains by ezrin binding and is strongly enhanced upon mutating Ser162 located in PDZ domain 2 of EBP50. Dephosphorylation of EBP50 at S162 is mediated by PP1α, a serine/threonine phosphatase localized at the microvillar base and involved in ezrin phosphocycling. Importantly, the binding of EBP50 to TMIGD1 enhances the dynamic turnover of EBP50 at microvilli in a Ser162 phosphorylation-dependent manner. We identify an adhesive complex at the microvillar base and propose a potential mechanism that regulates microvillar dynamics in enterocytes.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsAAamino acidE3KARPNHE3 kinase A regulatory proteinEBP50ERM-binding phosphoprotein of 50 kDaFRAPfluorescence recovery after photobleachingIFimmunofluorescenceJAM-AJunctional Adhesion Molecule-ANHERFNa+/H+ exchange regulatory cofactorPBMPDZ domain-binding motifPDZPostsynaptic density 95 - Discs Large - Zonula occludens-1TMIGD1Transmembrane and immunoglobulin domain-containing protein 1