title: Stimulation of the CLIP-170--dependent capture of membrane organelles by microtubules through fine tuning of microtubule assembly dynamics.
abstract: Cytoplasmic microtubules (MTs) continuously grow and shorten at their free plus ends, a behavior that allows them to capture membrane organelles destined for MT minus end-directed transport. In Xenopus melanophores, the capture of pigment granules (melanosomes) involves the +TIP CLIP-170, which is enriched at growing MT plus ends. Here we used Xenopus melanophores to test whether signals that stimulate minus end MT transport also enhance CLIP-170-dependent binding of melanosomes to MT tips. We found that these signals significantly (>twofold) increased the number of growing MT plus ends and their density at the cell periphery, thereby enhancing the likelihood of interaction with dispersed melanosomes. Computational simulations showed that local and global increases in the density of CLIP-170-decorated MT plus ends could reduce the half-time of melanosome aggregation by ~50%. We conclude that pigment granule aggregation signals in melanophores stimulate MT minus end-directed transport by the increasing number of growing MT plus ends decorated with CLIP-170 and redistributing these ends to more efficiently capture melanosomes throughout the cytoplasm.
authors: RD Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Alexis J
authors: AJ
authors: Lomakin
authors: Pavel
authors: P
authors: Kraikivski
authors: Irina
authors: I
authors: Semenova
authors: Kazuho
authors: K
authors: Ikeda
authors: Ilya
authors: I
authors: Zaliapin
authors: Jennifer S
authors: JS
authors: Tirnauer
authors: Anna
authors: A
authors: Akhmanova
authors: Vladimir
authors: V
authors: Rodionov
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D003198:Computer Simulation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008547:Melanophores / Q000187:drug effects / Q000378:metabolism; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology / Q000502:physiology; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D013449:Sulfonamides / Q000494:pharmacology; D014981:Xenopus
chemical_list: D002232:Carbocyanines; C405804:EB1 microtubule binding proteins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D013449:Sulfonamides; C089187:cyanine dye 3; C076744:cytoplasmic linker protein 170; D017868:Cyclic AMP-Dependent Protein Kinases; D008550:Melatonin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide