The Arp2/3 Complex Has Essential Roles in Vesicle Trafficking and Transcytosis in the Mammalian Small Intestine

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2015 Apr 3

PMID 25833710

Citations 28

Authors

Kang Zhou

Kaelyn D Sumigray

Terry Lechler

Affiliations

Soon will be listed here.

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.

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References

Chevrot M, Martin C, Passilly-Degrace P, Besnard P . Role of CD36 in oral and postoral sensing of lipids. Handb Exp Pharmacol. 2012; (209):295-307. DOI: 10.1007/978-3-642-24716-3_13. View

Tang V, Brieher W . α-Actinin-4/FSGS1 is required for Arp2/3-dependent actin assembly at the adherens junction. J Cell Biol. 2012; 196(1):115-30. PMC: 3255975. DOI: 10.1083/jcb.201103116. View

Verma S, Han S, Michael M, Gomez G, Yang Z, Teasdale R . A WAVE2-Arp2/3 actin nucleator apparatus supports junctional tension at the epithelial zonula adherens. Mol Biol Cell. 2012; 23(23):4601-10. PMC: 3510021. DOI: 10.1091/mbc.E12-08-0574. View

Duleh S, Welch M . Regulation of integrin trafficking, cell adhesion, and cell migration by WASH and the Arp2/3 complex. Cytoskeleton (Hoboken). 2012; 69(12):1047-58. PMC: 3582321. DOI: 10.1002/cm.21069. View

Rotty J, Wu C, Bear J . New insights into the regulation and cellular functions of the ARP2/3 complex. Nat Rev Mol Cell Biol. 2012; 14(1):7-12. DOI: 10.1038/nrm3492. View

Rath T, Kuo T, Baker K, Qiao S, Kobayashi K, Yoshida M . The immunologic functions of the neonatal Fc receptor for IgG. J Clin Immunol. 2012; 33 Suppl 1:S9-17. PMC: 3548031. DOI: 10.1007/s10875-012-9768-y. View

Kim I, Racz B, Wang H, Burianek L, Weinberg R, Yasuda R . Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities. J Neurosci. 2013; 33(14):6081-92. PMC: 3656411. DOI: 10.1523/JNEUROSCI.0035-13.2013. View

Zhou K, Muroyama A, Underwood J, Leylek R, Ray S, Soderling S . Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation. Proc Natl Acad Sci U S A. 2013; 110(40):E3820-9. PMC: 3791730. DOI: 10.1073/pnas.1308419110. View

Burd C, Cullen P . Retromer: a master conductor of endosome sorting. Cold Spring Harb Perspect Biol. 2014; 6(2). PMC: 3941235. DOI: 10.1101/cshperspect.a016774. View

10.

Madison B, Dunbar L, Qiao X, Braunstein K, Braunstein E, Gumucio D . Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J Biol Chem. 2002; 277(36):33275-83. DOI: 10.1074/jbc.M204935200. View

11.

Gournier H, Goley E, Niederstrasser H, Trinh T, Welch M . Reconstitution of human Arp2/3 complex reveals critical roles of individual subunits in complex structure and activity. Mol Cell. 2001; 8(5):1041-52. DOI: 10.1016/s1097-2765(01)00393-8. View

12.

Pepino M, Kuda O, Samovski D, Abumrad N . Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu Rev Nutr. 2014; 34:281-303. PMC: 4329921. DOI: 10.1146/annurev-nutr-071812-161220. View

13.

Stamnes M . Regulating the actin cytoskeleton during vesicular transport. Curr Opin Cell Biol. 2002; 14(4):428-33. DOI: 10.1016/s0955-0674(02)00349-6. View

14.

Rojas R, Apodaca G . Immunoglobulin transport across polarized epithelial cells. Nat Rev Mol Cell Biol. 2002; 3(12):944-55. DOI: 10.1038/nrm972. View

15.

Tyska M, Mooseker M . A role for myosin-1A in the localization of a brush border disaccharidase. J Cell Biol. 2004; 165(3):395-405. PMC: 2172191. DOI: 10.1083/jcb.200310031. View

16.

Saotome I, Curto M, McClatchey A . Ezrin is essential for epithelial organization and villus morphogenesis in the developing intestine. Dev Cell. 2004; 6(6):855-64. DOI: 10.1016/j.devcel.2004.05.007. View

17.

Verma S, Shewan A, Scott J, Helwani F, den Elzen N, Miki H . Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive contacts. J Biol Chem. 2004; 279(32):34062-70. DOI: 10.1074/jbc.M404814200. View

18.

Verges M, Luton F, Gruber C, Tiemann F, Reinders L, Huang L . The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol. 2004; 6(8):763-9. DOI: 10.1038/ncb1153. View

19.

Winter D, Choe E, Li R . Genetic dissection of the budding yeast Arp2/3 complex: a comparison of the in vivo and structural roles of individual subunits. Proc Natl Acad Sci U S A. 1999; 96(13):7288-93. PMC: 22078. DOI: 10.1073/pnas.96.13.7288. View

20.

Tyska M, Mackey A, Huang J, Copeland N, Jenkins N, Mooseker M . Myosin-1a is critical for normal brush border structure and composition. Mol Biol Cell. 2005; 16(5):2443-57. PMC: 1087248. DOI: 10.1091/mbc.e04-12-1116. View