The Planar Cell Polarity Protein Fat1 in Sertoli Cell Function

Area of Science:

• Cell Biology
• Reproductive Biology
• Molecular Biology

Background:

• The Fat atypical cadherin (Fat) and Dachsous cadherin-related protein (Dchs) form intercellular bridges at Sertoli cell interfaces, essential for testicular function.
• These bridges are supported by the nonreceptor Ser/Thr protein kinase Fjx1, a mechanism conserved from Drosophila studies.

Purpose of the Study:

• To investigate the role of Fat atypical cadherin 1 (Fat1) in Sertoli cell function and the integrity of the blood-testis barrier (BTB).
• To elucidate the molecular mechanisms by which Fat1 influences cytoskeletal dynamics and intercellular interactions within the testis.

Main Methods:

• Utilized RNA interference (RNAi) to knock down Fat1 expression in primary Sertoli cell cultures, mimicking the in vivo BTB.
• Performed functional assays to assess Sertoli cell tight junction (TJ) permeability and TJ integrity.

Main Results:

• Knockdown of Fat1 disrupted Sertoli cell function by altering actin and microtubule polymerization via the Fat1/Fjx1 complex.
• Fat1 was found to associate with β-catenin, α-N-catenin, and the Prickle 1/Vangl1 complex, indicating its role in planar cell polarity (PCP) pathways.
• Fat1 is integral to the stabilization of PCP at Sertoli cell interfaces, crucial for spermatogenesis.

Conclusions:

• Fat1 plays a critical role in maintaining the structural and functional integrity of the blood-testis barrier.
• The Fat1/Fjx1 complex modulates cytoskeletal dynamics, and Fat1's association with other PCP proteins stabilizes intercellular interactions essential for spermatogenesis.