TY - JOUR TI - Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes AU - Maxson, Michelle E AU - Naj, Xenia AU - O'Meara, Teresa R AU - Plumb, Jonathan D AU - Cowen, Leah E AU - Grinstein, Sergio A2 - Soldati-Favre, Dominique VL - 7 PY - 2018 DA - 2018/03/19 SP - e34798 C1 - eLife 2018;7:e34798 DO - 10.7554/eLife.34798 UR - https://doi.org/10.7554/eLife.34798 AB - Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae. KW - macrophage KW - Candida albicans KW - integrins KW - phagocytosis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -