title: Cytoskeletal control of CD36 diffusion promotes its receptor and signaling function.
abstract: The mechanisms that govern receptor coalescence into functional clusters--often a critical step in their stimulation by ligand--are poorly understood. We used single-molecule tracking to investigate the dynamics of CD36, a clustering-responsive receptor that mediates oxidized LDL uptake by macrophages. We found that CD36 motion in the membrane was spatially structured by the cortical cytoskeleton. A subpopulation of receptors diffused within linear confinement regions whose unique geometry simultaneously facilitated freedom of movement along one axis while increasing the effective receptor density. Co-confinement within troughs enhanced the probability of collisions between unligated receptors and promoted their clustering. Cytoskeleton perturbations that inhibited diffusion in linear confinement regions reduced receptor clustering in the absence of ligand and, following ligand addition, suppressed CD36-mediated signaling and internalization. These observations demonstrate a role for the cytoskeleton in controlling signal transduction by structuring receptor diffusion within membrane regions that increase their collision frequency.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Khuloud
authors.initials: K
authors.lastname: Jaqaman
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kuwata
authors.forename: Nicolas
authors.initials: N
authors.lastname: Touret
authors.forename: Richard
authors.initials: R
authors.lastname: Collins
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D052898:Optical Tweezers; D015398:Signal Transduction
chemical_list: D018955:CD36 Antigens; D000205:Actomyosin