MKS-NPHP module proteins control ciliary shedding at the transition zone

Area of Science:

• Cell Biology
• Cilia Biology
• Molecular Mechanisms

Background:

• Ciliary shedding is a fundamental cellular process observed across diverse organisms, crucial for cell cycle progression and neurogenesis.
• The precise molecular mechanisms governing ciliary shedding remain largely unknown, despite its occurrence distal to the transition zone (TZ) in various models.
• Transition zone (TZ) proteins, including Meckel Gruber syndrome (MKS), Nephronophtysis (NPHP), Centrosomal protein of 290 kDa (CEP290), and Retinitis pigmentosa GTPase regulator-Interacting Protein 1-Like Protein (RPGRIP1L), are known to be vital for TZ assembly and function.

Purpose of the Study:

• To investigate the role of conserved transition zone (TZ) proteins in regulating ciliary shedding.
• To determine if specific TZ proteins influence the process of deciliation in unicellular organisms.

Main Methods:

• Studied the function of five TZ proteins: Transmembrane protein 107 (TMEM107), Transmembrane protein 216 (TMEM216), CEP290, RPGRIP1L, and NPHP4 in the model organism Paramecium.
• Utilized protein depletion techniques to assess the impact on ciliary shedding.
• Examined protein localization within the cilia, specifically at the TZ, using microscopy.

Main Results:

• All five investigated TZ proteins localize to the distal part of the TZ in growing cilia with 9-fold symmetry.
• Depletion of TMEM216 (MKS2) and TMEM107 leads to constant, spontaneous ciliary shedding.
• Depletion of NPHP4, CEP290, or RPGRIP1L inhibits chemically induced (Ca2+/EtOH) deciliation.

Conclusions:

• This study provides the first evidence that conserved TZ proteins play a critical role in regulating ciliary shedding.
• The findings suggest distinct functions for different TZ proteins in either initiating or preventing deciliation.
• Opens new avenues for understanding the physiology of motile cilia and associated disorders.