title: The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.
abstract: The Arp2/3 complex is the only known nucleator of branched F-actin filaments. Work in cultured cells has established a wide array of functions for this complex in controlling cell migration, shape, and adhesion. However, loss of Arp2/3 complex function in tissues has yielded cell type-specific phenotypes. Here we report essential functions of the Arp2/3 complex in the intestinal epithelium. The Arp2/3 complex was dispensable for intestinal development, generation of cortical F-actin, and cell polarity. However, it played essential roles in vesicle trafficking. We found that in the absence of ArpC3, enterocytes had defects in the organization of the endolysosomal system. These defects were physiologically relevant, as transcytosis of IgG was disrupted, lipid absorption was perturbed, and neonatal mice died within days of birth. These data highlight the important roles of the Arp2/3 complex in vesicle trafficking in enterocytes and suggest that defects in cytoplasmic F-actin assembly by the Arp2/3 complex, rather than cortical pools, underlie many of the phenotypes seen in the mutant small intestine.
authors.affiliation: Department of Dermatology and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Dermatology and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Kaelyn D
authors.initials: KD
authors.lastname: Sumigray
authors.affiliation: Department of Dermatology and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710 terry.lechler@duke.edu.
authors.forename: Terry
authors.initials: T
authors.lastname: Lechler
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000818:Animals; D011992:Endosomes / Q000378:metabolism / Q000502:physiology*; D055786:Gene Knockout Techniques; D007074:Immunoglobulin G / Q000378:metabolism; D007408:Intestinal Absorption / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism* / Q000502:physiology; D050356:Lipid Metabolism; D051379:Mice; D057900:Transcytosis / Q000235:genetics / Q000502:physiology*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C513333:Arpc3 protein, mouse; D007074:Immunoglobulin G
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