Rahmani, Shapour et al. (2021) International Worm Meeting "Investigating the function of TAT proteins in lipid transport within ciliated neurons."

Rahmani, Shapour, Tuck, Simon

[International Worm Meeting, 2021]

Cilia have protein and lipid compositions that are distinct from that of the cells from which they protrude. Although a clear picture exists of how protein transport occurs in cilia, the mechanisms regulating lipid composition are not presently understood. Furthermore, much remains to be learned about how changes in lipid distribution affect cilium function. The major phospholipids in plasma membranes are phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylchoine (PC) and phosphatidylinositol (PI). These phospholipids are not symmetrically distributed in the leaflets that make up membrane bilayers: in particular, PC is largely confined to the outer (exofacial) leaflet while PE, PS and PI are mostly confined to the inner. These asymmetries are maintained by the movement of phospholipids through the cell membranes catalyzed by transamphipathic aminophospholipid translocases belonging to the P4 family of transmembrane ATPases. C. elegans has six translocase genes, tat-1 - tat-6. We have found that tat-6 is specifically expressed in a subset of C. elegans ciliated neurons and that TAT-6 protein accumulates in cilia. To study the function of TAT-6 and that other translocases in lipid transport in C. elegans ciliated neurons, we developed a technique to allow labelling of cilia with lipids. For the first time in C. elegans ciliary research we used fusogenic liposomes to deliver fluorescently labelled lipids to the membranes of ciliated neurons. We have used this technique to study the roles of all the TAT proteins in this organism in maintaining the distinct lipid composition and lipid asymmetry in ciliary membranes. Our experiments revealed that TAT-5 and TAT-1 translocase activities primarily promote the transport of phosphatidylethanolamine (PE) and phosphatidylserine (PS) respectively whereas TAT-6 has an overlapping function in transporting both PS and PE. Mutants lacking pad-1, which encodes a cofactor for TAT-5, also show defects in PE transport. tat-5 and tat-6 mutants display defects in behaviours mediated by ciliated neurons. Overall, our investigation indicates that the regulation of lipid asymmetry and phospholipid transport is required for cilia to function properly in C. elegans.

Rogalski TM et al. (2000) West Coast Worm Meeting "Cellular and developmental events required to generate functional muscle in C. elegans."

Mullen GP, Moerman DG, Rahmani P, Norman KR, Rogalski TM, Cordes S

[West Coast Worm Meeting, 2000]

In C. elegans a physical linkage between the myofilament lattice of the body wall muscle and the cuticle is required to allow myofilament contraction to result in the movement of the animal. This complex linkage system is composed of integrin containing adhesion-complexes within the body wall muscle cells that anchor the myofibrils to the muscle cell membrane, a specialized basement membrane underlying the muscle quadrant, and hemidesmosomal-like structures present in the epidermis. The epidermis has specialized faces, one to anchor the epidermis to the basement membrane and the other to secrete and anchor the cuticle. The nematode provides a very elegant system to study the interaction between the body wall muscle and the epidermis during development. Through genetic and molecular approaches we have identified (1) several components involved in assembly, localization, and maintenance of adhesion complexes within muscle (the unc-52, unc-97, unc-112, dim-1 and spc-1 gene products), (2) components that are involved in structuring the underlying basement membranes (the let-268 gene product), and (3) others that function in regulating epidermal attachment structures (the unc-23 gene product). The role of these molecules in muscle and epidermal development during C. elegans morphogenesis will be described. For more information on unc-23 and unc-97 see posters by P. Rahmani and S. Cordes, respectively.