title: A Rab11a-enriched subapical membrane compartment regulates a cytoskeleton-dependent transcytotic pathway in secretory epithelial cells of the lacrimal gland.
abstract: Despite observations that the lacrimal gland has been identified as the principal source of dimeric immunoglobulin A (dIgA) in tears, the mechanism used by lacrimal gland acinar cells (LGACs) to transcytose dIgA produced by interstitial plasma cells is not well-characterized. This study identifies a transcytotic pathway in LGACs regulated by Rab11a for polymeric immunoglobulin receptor (pIgR) and dIgA. EGFP-tagged Rab11a expressed in primary LGACs labeled a unique membrane compartment of comparable localization to endogenous Rab11a beneath the apical plasma membrane. This compartment was enriched in pIgR and clearly distinct from the regulated secretory pathway. Comparison of dIgA uptake in LGACs expressing wild type and dominant negative EGFP-Rab11a showed that the rapid exocytosis of dIgA was inhibited in acini expressing the dominant-negative protein, which additionally redistributed subapical pIgR. The trafficking of EGFP-Rab11a-enriched vesicles was regulated by microtubule-based and myosin Vb motors at distinct steps. Our data suggest that Rab11a is a crucial regulator of dIgA trafficking in primary acinar secretory epithelial cells and further support a role for microtubules, cytoplasmic dynein, actin filaments and myosin Vb in the maintenance of the Rab11a compartment in this primary secretory epithelial cell.
authors: Department of Pharmacology and Pharmaceutical Sciences, 1985 Zonal Avenue, USC School of Pharmacy, University of Southern California, Los Angeles, CA 90033,  USA.
authors: Shi
authors: S
authors: Xu
authors: Maria
authors: M
authors: Edman
authors: Mubashera S
authors: MS
authors: Kothawala
authors: Guoyong
authors: G
authors: Sun
authors: Lilian
authors: L
authors: Chiang
authors: Austin
authors: A
authors: Mircheff
authors: Lixin
authors: L
authors: Zhu
authors: Curtis
authors: C
authors: Okamoto
authors: Sarah
authors: S
authors: Hamm-Alvarez
mesh_terms: D061354:Acinar Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D011817:Rabbits; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism; D013666:Tears / Q000276:immunology / Q000378:metabolism; D057900:Transcytosis / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins