The primary cilium is a highly conserved organelle housing specialized molecules responsible for receiving and processing extracellular signals. A recently discovered property shared across many cilia is the ability to release small vesicles called ectosomes, which are used for exchanging protein and genetic material among cells. In this study, we report a novel role for ciliary ectosomes in building the elaborate photoreceptor outer segment filled with hundreds of tightly packed "disc" membranes. We demonstrate that the photoreceptor cilium has an innate ability to release massive amounts of ectosomes. However, this process is suppressed by the disc-specific protein peripherin, which enables retained ectosomes to be morphed into discs. This new function of peripherin is performed independently from its well-established role in maintaining the high curvature of disc edges, and each function is fulfilled by a separate part of peripherin's molecule. Our findings explain how the outer segment structure evolved from the primary cilium to provide photoreceptor cells with vast membrane surfaces for efficient light capture.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412563 | PMC |
http://dx.doi.org/10.1083/jcb.201608081 | DOI Listing |
J Cell Biol
April 2025
Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells.
View Article and Find Full Text PDFPrimary cilia play a pivotal role in cellular signaling and development and disruptions in ciliary form and/or function leads to human ciliopathies. Here, we examine the role of , a key component of the intraflagellar transport-A complex, in mouse forebrain development using a null allele. Our findings reveal significant microcephaly in homozygous mutants is caused by disrupted neural progenitor proliferation and differentiation.
View Article and Find Full Text PDFBackground And Purpose: Polycystins (PKD2, PKD2L1) are voltage-gated and Ca -modulated members of the transient receptor potential (TRP) family of ion channels. Loss of PKD2L1 expression results in seizure-susceptibility and autism-like features in mice, whereas variants in PKD2 cause autosomal dominant polycystic kidney disease. Despite decades of evidence clearly linking their dysfunction to human disease and demonstrating their physiological importance in the brain and kidneys, the polycystin pharmacophore remains undefined.
View Article and Find Full Text PDFMicrocephaly affects 1 in 2,500 babies per year. Primary microcephaly results from aberrant neurogenesis leading to a small brain at birth. This is due to altered patterns of proliferation and/or early differentiation of neurons.
View Article and Find Full Text PDFNat Commun
January 2025
Cluster of Excellence Physics of Life, TUD Dresden University of Technology, 01062, Dresden, Germany.
Cilia assembly and function rely on the bidirectional transport of components between the cell body and ciliary tip via Intraflagellar Transport (IFT) trains. Anterograde and retrograde IFT trains travel along the B- and A-tubules of microtubule doublets, respectively, ensuring smooth traffic flow. However, the mechanism underlying this segregation remains unclear.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!