Zhang Caiyun, Li Chunman, Siu Gavin Ka Yu, Luo Xiaomin, Yu Sidney
School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, China.
Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, China.
Front Cell Dev Biol. 2020 Mar 17;8:148. doi: 10.3389/fcell.2020.00148. eCollection 2020.
The transport protein particle (TRAPP) complex was initially identified as a tethering factor for COPII vesicle. Subsequently, three forms (TRAPPI, II, and III) have been found and TRAPPIII has been reported to serve as a regulator in autophagy. This study investigates a new role of mammalian TRAPPIII in ciliogenesis. We found a ciliopathy protein, oral-facial-digital syndrome 1 (OFD1), interacting with the TRAPPIII-specific subunits TRAPPC8 and TRAPPC12. TRAPPC8 is necessary for the association of OFD1 with pericentriolar material 1 (PCM1). Its depletion reduces the extent of colocalized signals between OFD1 and PCM1, but does not compromise the structural integrity of centriolar satellites. The interaction between TRAPPC8 and OFD1 inhibits that between OFD1 and TRAPPC12, suggesting different roles of TRAPPIII-specific subunits in ciliogenesis and explaining the differences in cilium lengths in TRAPPC8-depleted and TRAPPC12-depleted hTERT-RPE1 cells. On the other hand, TRAPPC12 depletion causes increased ciliary length because TRAPPC12 is required for the disassembly of primary cilia. Overall, this study has revealed different roles of TRAPPC8 and TRAPPC12 in the assembly of centriolar satellites and demonstrated a possible tethering role of TRAPPIII during ciliogenesis.
转运蛋白颗粒（TRAPP）复合体最初被鉴定为COPII囊泡的拴系因子。随后，发现了三种形式（TRAPPI、II和III），并且据报道TRAPPIII在自噬中起调节作用。本研究调查了哺乳动物TRAPPIII在纤毛发生中的新作用。我们发现一种纤毛病蛋白，口面指综合征1（OFD1），与TRAPPIII特异性亚基TRAPPC8和TRAPPC12相互作用。TRAPPC8是OFD1与中心粒周物质1（PCM1）结合所必需的。它的缺失减少了OFD1和PCM1之间共定位信号的程度，但不影响中心粒卫星的结构完整性。TRAPPC8和OFD1之间的相互作用抑制了OFD1和TRAPPC12之间的相互作用，这表明TRAPPIII特异性亚基在纤毛发生中具有不同作用，并解释了TRAPPC8缺失和TRAPPC12缺失的hTERT-RPE1细胞中纤毛长度的差异。另一方面，TRAPPC12的缺失导致纤毛长度增加，因为TRAPPC12是初级纤毛解聚所必需的。总体而言，本研究揭示了TRAPPC8和TRAPPC12在中心粒卫星组装中的不同作用，并证明了TRAPPIII在纤毛发生过程中可能具有拴系作用。
