Constructing the distinct subcellular environment of the cilium relies in a large part upon intraflagellar transport (IFT) proteins, which traffic cargo both to and within the cilium. However, evidence from the last 10 years suggests that IFT alone is not sufficient to generate the ciliary environment. One essential factor is UNC119, which interacts with known IFT molecular switches to transport ciliary cargos. Despite its apparent importance in ciliary trafficking though, human UNC119 mutations have only rarely been associated with diseases commonly linked with ciliopathies. This review will outline the trafficking pathways required for constructing the cilium by highlighting UNC119's role and the complexities involved in ciliary trafficking. Finally, despite important roles for UNC119 in cilia, UNC119 proteins also interact with non-ciliary proteins to affect other cellular processes.
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http://dx.doi.org/10.1016/j.ejcb.2017.09.001 | DOI Listing |
T-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.
View Article and Find Full Text PDFPLoS Biol
November 2024
Department of Neurobiology, University of California San Diego, La Jolla, California, United States of America.
Intraflagellar transport (IFT) is essential for both ciliary structure and function. A new study in PLOS Biology reveals how IFT-mediated trafficking and ciliary morphology differentially influence chemosensory responses between neuronal types and among co-expressed receptors.
View Article and Find Full Text PDFPLoS Biol
November 2024
Department of Biology, Brandeis University, Waltham, Massachusetts, United States of America.
Sensory neurons contain morphologically diverse primary cilia that are built by intraflagellar transport (IFT) and house sensory signaling molecules. Since both ciliary structural and signaling proteins are trafficked via IFT, it has been challenging to decouple the contributions of IFT and cilia structure to neuronal responses. By acutely inhibiting IFT without altering cilia structure and vice versa, here we describe the differential roles of ciliary trafficking and sensory ending morphology in shaping chemosensory responses in Caenorhabditis elegans.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
The primary cilium is a paradigmatic subcellular compartment at the nexus of numerous cellular and morphogenetic pathways. The tubby family protein TULP3 acts as an adapter of the intraflagellar transport complex A in transporting integral membrane and membrane-associated lipidated proteins into cilia. However, the mechanisms by which TULP3 coordinates ciliary transport of diverse cargoes is not well understood.
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