EHD1 promotes CP110 ubiquitination by centriolar satellite delivery of HERC2 to the mother centriole

Abstract

Primary cilia are sensory organelles that coordinate diverse signaling pathways, controlling development and homeostasis. Progression beyond the early steps of ciliogenesis requires the removal of a distal end protein, CP110, from the mother centriole, a process mediated by Eps15 Homology Domain protein 1 (EHD1). We show that EHD1 regulates CP110 ubiquitination during ciliogenesis, and identify two E3 ubiquitin ligases, HECT domain and RCC1‐like domain 2 (HERC2) and mindbomb homolog 1 (MIB1), that interact with and ubiquitinate CP110. We determined that HERC2 is required for ciliogenesis and localizes to centriolar satellites, which are peripheral aggregates of centriolar proteins known to regulate ciliogenesis. We reveal a role for EHD1 in the transport of centriolar satellites and HERC2 to the mother centriole during ciliogenesis. Taken together, our work showcases a mechanism whereby EHD1 controls centriolar satellite movement to the mother centriole, thus delivering the E3 ubiquitin ligase HERC2 to promote CP110 ubiquitination and degradation. image Primary cilia are sensory organelles that coordinate diverse signaling pathways, controlling development and homeostasis. The endocytic regulatory protein, EHD1, facilitates centriolar satellite movement to the mother centriole leading to ubiquitination and degradation of the capping protein, CP110, thereby promoting primary ciliogenesis. EHD1 promotes centriolar satellite transport to the mother centriole. HERC2 is a centriolar satellite E3 ligase required for ubiquitination and degradation of CP110. EHD1 depletion impedes recruitment of centriolar satellites and HERC2 to the centrosome, causing CP110 retention on the mother centriole and impaired ciliogenesis.