Septin-mediated RhoA activation engages the exocyst complex to recruit the cilium transition zone

Area of Science:

• Cell Biology
• Molecular Biology
• Cilia Biology

Background:

• Septins are GTPases involved in various cellular processes, including cytokinesis and membrane dynamics.
• Their specific roles in ciliogenesis, the formation of cilia, remain poorly understood.
• Cilia are critical for cellular signaling and function, and defects are linked to various diseases.

Purpose of the Study:

• To elucidate the function of SEPTIN9 in the process of ciliogenesis.
• To identify the molecular mechanisms by which SEPTIN9 regulates cilia formation.
• To investigate the relationship between SEPTIN9, RhoA signaling, and ciliogenesis.

Main Methods:

• Utilized cell-based assays to study SEPTIN9 function in ciliogenesis.
• Investigated the interaction between SEPTIN9, ARHGEF18, and RhoA signaling.
• Employed techniques to assess protein localization, including basal body-targeted proteins and exocyst subunits.
• Examined the impact of SEPTIN9 depletion on transition zone protein accumulation.

Main Results:

• SEPTIN9 directly binds and activates ARHGEF18, a guanine nucleotide exchange factor for RhoA.
• SEPTIN9 depletion disrupts ciliogenesis and causes mislocalization of the exocyst subunit SEC8.
• Restoring RhoA signaling at the cilium can rescue ciliary defects caused by SEPTIN9 depletion.
• SEPTIN9 and the exocyst complex are required for the recruitment of transition zone proteins RPGRIP1L and TCTN2.

Conclusions:

• SEPTIN9 is a key regulator of ciliogenesis, acting through the RhoA/exocyst pathway.
• SEPTIN9 facilitates the recruitment of transition zone proteins via Golgi-derived vesicles.
• This mechanism is essential for the proper formation of primary cilia.