Smoothelin-like 2 Inhibits Coronin-1B to Stabilize the Apical Actin Cortex during Epithelial Morphogenesis

Area of Science:

• Cell Biology
• Developmental Biology
• Biochemistry

Background:

• The actin cortex is vital for cell differentiation and function, requiring remodeling during development.
• Developing epithelial cells form a dense apical actin cortex for barrier and exchange functions, influenced by extracellular cues.
• Regulation of apical actin cortex assembly during epithelial morphogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of Smoothelin-like 2 (SMTNL2) in the maturation of the apical actin cortex during epithelial development.
• To elucidate the molecular mechanisms by which SMTNL2 regulates actin dynamics and epithelial morphogenesis.

Main Methods:

• Analysis of SMTNL2 expression during epithelial development.
• Assessment of SMTNL2 function in epithelial cells using SMTNL2-deficient models.
• Biochemical assays to determine SMTNL2 interaction with actin filaments and coronin-1B.
• Identification of SMTNL2 proximal interactome.

Main Results:

• SMTNL2 is induced during epithelial development and localizes to the apical and junctional actin cortex.
• SMTNL2 deficiency causes apical membrane herniations, indicating defects in the actin cortex.
• SMTNL2 binds actin filaments, slows apical actin turnover, and inhibits coronin-1B activity.
• SMTNL2 stabilizes the apical cortex by binding to coronin-1B and negating its function.

Conclusions:

• SMTNL2 plays a critical role in stabilizing the apical actin cortex during epithelial morphogenesis.
• SMTNL2 regulates actin dynamics by modulating actin turnover and inhibiting coronin-1B.
• This study reveals a novel mechanism controlling cellular cortex development essential for epithelial function.