| Autor: |
Hartmann, Christian, Thüring, Eva-Maria, Greune, Lilo, Michels, Birgitta E., Pajonczyk, Denise, Leußink, Sophia, Brinkmann, Frauke, Glaesner-Ebnet, Mark, Wardelmann, Eva, Zobel, Thomas, Schmidt, M. Alexander, Janssen, Klaus-Peter, Gerke, Volker, Ebnet, Klaus |
| Předmět: |
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| Zdroj: |
Science Signaling; 9/13/2022, Vol. 15 Issue 751, p1-18, 18p |
| Abstrakt: |
Intestinal epithelial cells absorb nutrients through the brush border, composed of dense arrays of highly ordered microvilli at their apical membranes. A protocadherin-based intermicrovillar adhesion complex localized at microvilli tips mediates microvilli packing and organization. Here, we identified a second adhesion complex localized at the proximal base region of microvilli. This complex contained the immunoglobulin superfamily member TMIGD1, which directly interacted with the microvillar scaffolding proteins EBP50 and E3KARP. Complex formation with EBP50 required the activation of EBP50 by the actin-binding protein ezrin and was enhanced by the dephosphorylation of Ser162 in the PDZ2 domain of EBP50 by the phosphatase PP1α. Binding of the EBP50-ezrin complex to TMIGD1 enhanced the dynamic turnover of EBP50 at microvilli. Enterocyte-specific inactivation of Tmigd1 in mice resulted in microvillar blebbing, loss of intermicrovillar adhesion, and perturbed brush border formation. Thus, we identified a second adhesion complex in microvilli and propose a mechanism that promotes microvillar formation and dynamics. TMIGD1 brings up the brush border: Cellular structures called microvilli form at the apical membrane of intestinal epithelial cells through a process dependent on the intermicrovillar adhesion complex (IMAC) located at the tips of microvilli. These microvilli form the intestinal brush border to mediate nutrient absorption. Hartmann et al. identified a second adhesion complex at the base of microvilli centered around the adhesion molecule TMIGD1, which was required for microvilli formation and an intact brush border. TMIGD1 was recruited to the brush border by the scaffolding proteins E3KARP and EBP50. Activation by the actin-binding protein ezrin enabled the EBP50-TMIGD1 association. EBP50 acted as a scaffold for both ezrin and the phosphatase PP1α, which promoted the EBP50-TMIGD1 interaction. These findings characterize how TMIGD1 nucleates a complex that is important for brush border formation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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