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Biology subjects

Ball, D. G.

Publications and source records attributed to Ball, D. G..

2 recordsLinked to original sources

Rho/ROCK-dependent actomyosin contractility drives extracellular vesicle release from the cilium

The release of extracellular vesicles (EV) from the primary cilium is a conserved process observed in many cell types. It serves as a rapid and efficient mechanism to release select proteins from the cilium, which can be used for either intercellular communication or membrane material disposal. Previous studies have shown that the release of EVs from the cilium relies on the actin cytoskeleton and proposed several molecular mechanisms that may perform this function. Using the model of IMCD3 cells, we now demonstrate that this process relies on actomyosin contractility supported by non-muscle myosin IIA acting downstream of the RhoA-ROCK signaling pathway. We further showed that the cilia of these cells release EVs independently of de novo actin polymerization, which we confirmed using an in vivo model of mutant photoreceptor cells that release massive amounts of vesicles from their cilia instead of elaborating into light-sensitive outer segment membrane structures.

cell biology↗

The tetraspanin disc proteins, peripherin-2 and ROM1, facilitate CNG channel localization to the rod outer segment

The light-responsive outer segment of rod photoreceptors is composed of two distinct membrane subdomains: discs and the plasma membrane. We investigate how the disc protein peripherin-2 is engaged in CNG channel delivery to the outer segment. Instead of forming outer segments, peripherin-2 knockout (Rds-/-) photoreceptors release ciliary ectosomes, in which CNG channel levels are markedly reduced relative to other outer segment proteins. This is intriguing as downregulation of the CNG channel is not a general feature of degenerative mouse models with dysmorphic outer segments. Overexpression of the {beta}1-subunit of CNG in Rds-/- rods reveals that the majority is trapped in intracellular membranes, but is restored to the outer segment by co-expressing peripherin-2. We test peripherin-2 chimeras containing either the N-terminus, tetraspanin core, or C-terminus and find that the tetraspanin domain is sufficient to localize CNG{beta}1 to the outer segment. We further show that the membrane remodeling function of the tetraspanin domain facilitates this process by the redundant action of the tetraspanin domain from ROM1 and the reemergence of the endogenous CNG channel in aged Rds-/- rods that have produced ciliary membrane protrusions.

cell biology↗