Galectin-3, a novel centrosome-associated protein, required for epithelial morphogenesis

Area of Science:

• Cell Biology
• Developmental Biology
• Biochemistry

Background:

• Galectin-3, a beta-galactoside-binding protein, is vital for epithelial tissue homeostasis and cancer progression.
• Previous studies indicated galectin-3's role in membrane domain identity, suggesting involvement in epithelial polarity.

Purpose of the Study:

• To investigate galectin-3's role in the early stages of epithelial renal cell polarization.
• To examine the effects of galectin-3 depletion on microtubule networks, membrane compartmentalization, and centrosome biology in vitro and in vivo.

Main Methods:

• Utilized three-dimensional cultures of Madin-Darby canine kidney (MDCK) cells.
• Employed galectin-3 null mutant mouse kidneys for in vivo analysis.
• Applied immunological and biochemical approaches to study protein associations.

Main Results:

• Galectin-3 depletion caused severe disruptions in the microtubule network and membrane compartmentalization.
• Absence of galectin-3 led to defects in primary cilium morphology, resulting in longer and unusually shaped cilia.
• Endogenous galectin-3 associates with basal bodies and centrosomes, interacting with proteins like centrin-2 during polarization.
• Galectin-3-depleted cells exhibited numerous centrosome-like structures, indicating a role in centrosome formation/stability.

Conclusions:

• Galectin-3 is essential for maintaining epithelial cell polarity and proper microtubule organization.
• Galectin-3 plays a critical role in centrosome biology, influencing their formation and stability during epithelial morphogenesis.
• These findings establish galectin-3 as a key regulator of epithelial development through its impact on centrosome function.