Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. (17/50)

Clusters of CD59, a glycosylphosphatidylinositol-anchored receptor (GPI-AR), with physiological sizes of approximately six CD59 molecules, recruit Galphai2 and Lyn via protein-protein and raft interactions. Lyn is activated probably by the Galphai2 binding in the same CD59 cluster, inducing the CD59 cluster's binding to F-actin, resulting in its immobilization, termed stimulation-induced temporary arrest of lateral diffusion (STALL; with a 0.57-s lifetime, occurring approximately every 2 s). Simultaneous single-molecule tracking of GFP-PLCgamma2 and CD59 clusters revealed that PLCgamma2 molecules are transiently (median = 0.25 s) recruited from the cytoplasm exclusively at the CD59 clusters undergoing STALL, producing the IP(3)-Ca(2+) signal. Therefore, we propose that the CD59 cluster in STALL may be a key, albeit transient, platform for transducing the extracellular GPI-AR signal to the intracellular IP(3)-Ca(2+) signal, via PLCgamma2 recruitment. The prolonged, analogue, bulk IP(3)-Ca(2+) signal, which lasts for more than several minutes, is likely generated by the sum of the short-lived, digital-like IP(3) bursts, each created by the transient recruitment of PLCgamma2 molecules to STALLed CD59.  (+info)

Mice expressing a mutant Krt75 (K6hf) allele develop hair and nail defects resembling pachyonychia congenita. (18/50)

KRT75 (formerly known as K6hf) is one of the isoforms of the keratin 6 (KRT6) family located within the type II cytokeratin gene cluster on chromosome 12 of humans and chromosome 15 of mice. KRT75 is expressed in the companion layer and upper germinative matrix region of the hair follicle, the medulla of the hair shaft, and in epithelia of the nail bed. Dominant mutations in members of the KRT6 family, such as in KRT6A and KRT6B cause pachyonychia congenita (PC) -1 and -2, respectively. To determine the function of KRT75 in skin appendages, we introduced a dominant mutation into a highly conserved residue in the helix initiation peptide of Krt75. Mice expressing this mutant form of Krt75 developed hair and nail defects resembling PC. This mouse model provides in vivo evidence for the critical roles played by Krt75 in maintaining hair shaft and nail integrity. Furthermore, the phenotypes observed in our mutant Krt75 mice suggest that KRT75 may be a candidate gene for screening PC patients who do not exhibit obvious mutations in KRT6A, KRT6B, KRT16, or KRT17, especially those with extensive hair involvement.  (+info)

Unique features of spermiogenesis in the Musky Rat-kangaroo: reflection of a basal lineage or a distinct fertilization process? (19/50)

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Native 3D intermediates of membrane fusion in herpes simplex virus 1 entry. (20/50)

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Stimulated emission depletion (STED) nanoscopy of a fluorescent protein-labeled organelle inside a living cell. (21/50)

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Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion. (22/50)

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Kinetochore-microtubule attachment relies on the disordered N-terminal tail domain of Hec1. (23/50)

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Enantioselective synthesis of (+)-chamaecypanone C: a novel microtubule inhibitor. (24/50)

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