A Rab11a-enriched subapical membrane compartment regulates a cytoskeleton-dependent transcytotic pathway in secretory epithelial cells of the lacrimal gland

Xu, Shi‐Hai; Edman, Maria C.; Kothawala, Mubashera S.; Sun, George; Chiang, Lilian; Mircheff, Austin K.; Zhu, Lixin; Okamoto, Curtis T.

doi:10.1242/jcs.088906

Cited by 20 publications

(40 citation statements)

References 43 publications

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“…RAB11A regulates membrane trafficking into and out of the recycling endosome (Tarbutton et al 2005). It has been implicated in the recycling of membrane components and transcytosis of molecules in polarized epithelia (Casanova et al 1999, Xu et al 2011. Our observation that nectin 2 positive vesicles that also label for the recycling endosomal marker RAB11A occur at newly forming ESs with early spermatids is the first indication that junction proteins internalized at TBCs may be recycled to newly forming junctions elsewhere in the epithelium (Fig.…”

Section: Discussionmentioning

confidence: 53%

Internalization of adhesion junction proteins and their association with recycling endosome marker proteins in rat seminiferous epithelium

Young¹,

Takai²,

Kojic³

et al. 2012

Reproduction

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Tubulobulbar complexes (TBCs) are elaborate cytoskeleton-related structures that are formed in association with intercellular junctions in the seminiferous epithelium. They consist of a cylindrical double-membrane core composed of the plasma membranes of the two attached cells, cuffed by a dendritic network of actin filaments. TBCs are proposed to be subcellular machines that internalize intercellular junctions during the extensive junction remodeling that occurs during spermatogenesis. At the apical sites of attachment between Sertoli cells and spermatids, junction disassembly is part of the sperm release mechanism. In this study, we used immunological probes to explore junction internalization and recycling at apical TBCs in the rat seminiferous epithelium. We demonstrate that b1-integrin and nectin 2 were concentrated at the ends of TBCs and for the first time show that the early endosome marker RAB5A was also distinctly localized at the ends of TBCs that appear to be the 'bulbar' regions of the complexes. Significantly, we also demonstrate that the 'long-loop' recycling endosome marker RAB11A was co-distributed with nectin 2 at junctions with early spermatids deeper in the epithelium. Our results are consistent with the hypothesis that TBCs associated with late spermatids internalize adhesion junctions and also indicate that some of the internalized junction proteins may be recycled to form junctions with the next generation of spermatids.

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Section: Discussionmentioning

confidence: 53%

Internalization of adhesion junction proteins and their association with recycling endosome marker proteins in rat seminiferous epithelium

Young¹,

Takai²,

Kojic³

et al. 2012

Reproduction

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“…1C,D), suggesting that EGFP did not interfere with the appropriate localization of hpIgR-EGFP. In addition, we have previously noted that endogenous pIgR is extensively colocalized with exogenous EGFP-Rab11a (Xu et al, 2011); conversely, hpIgR-EGFP showed substantial colocalization with endogenous Rab11 (Fig. 1E).…”

Section: Expression Of Fluorescent Pigr Constructs In Primary Lgacsmentioning

confidence: 52%

“…Adenovirus (Ad) constructs are capable of transducing rabbit primary LGACs at efficiencies .80% (Jerdeva et al, 2005;Evans et al, 2008;Chiang et al, 2011;Xu et al, 2011). We constructed Ad encoding human pIgR fused with enhanced green fluorescent protein (EGFP) at the C9 terminus of the cytoplasmic domain of the hpIgR (hpIgR-EGFP) (Fig.…”

Section: Expression Of Fluorescent Pigr Constructs In Primary Lgacsmentioning

confidence: 99%

“…LGACs use both the regulated secretory pathway and the transcytotic pathway to transport proteins into tear fluid (Evans et al, 2008;Chiang et al, 2011;Xu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Apart from the regulated secretory pathway, we have characterized a transcytotic pathway in LGACs for mediating transcytosis of pIgR and dIgA from the BLM to the APM (Xu et al, 2011). Key molecular regulators of the transcytotic pathway in LGACs are Rab11a, the small GTPase involved in regulating membrane recycling and transcytosis in other cells (Lapierre et al, 2001;Volpicelli et al, 2002;Ducharme et al, 2007;Wang et al, 2008), and myosin Vb (Wilcke et al, 2000;Lapierre et al, 2001;Volpicelli et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Polymeric immunoglobulin receptor traffics through two distinct apically targeted pathways in primary lacrimal gland acinar cells

Evans

et al. 2013

Journal of Cell Science

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SummaryThe polymeric immunoglobulin receptor (pIgR) mediates transcytosis of dimeric immunoglobulin A (dIgA) and its release into mucosal secretions. The present study reveals the complexity of the trafficking of pIgR to the apical plasma membrane in epithelial cells with exocrine secretory functions; in rabbit lacrimal gland acinar cells (LGACs), trafficking of pIgR involves both the transcytotic pathway and one arm of the regulated secretory pathway. By specifically tracking pIgR endocytosed from the basolateral membrane, we show here that the Rab11a-regulated transcytotic pathway mediates the basal-to-apical transport of pIgR, and that pIgR sorted into the transcytotic pathway does not access the regulated secretory pathway. However, previous work in LGACs expanded in the present study has shown that some pIgR is localized to Rab3D-enriched mature secretory vesicles (SVs). Myosin Vb and myosin Vc motors modulate release of proteins from the Rab11a-regulated transcytotic pathway and the Rab3D-enriched secretory pathway in LGACs, respectively. Confocal fluorescence microscopy and biochemical assays showed that inhibition of myosin Vb and myosin Vc activity by overexpression of their dominant-negative mutants each significantly but differentially impaired aspects of apically targeted pIgR trafficking and secretory component release, suggesting that these motors function to regulate pIgR trafficking in both the transcytotic and exocytotic pathways. Intriguingly, a second mature SV population enriched in Rab27b was devoid of pIgR cargo, suggesting the specialization of Rab3D-enriched mature SVs to carry a particular subset of cargo proteins from the trans-Golgi network to the apical plasma membrane.

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The Polymeric Immunoglobulin Receptor

Kaetzel

2013

Encyclopedia of Life Sciences

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Secretory Immunoglobulin A (SIgA) antibodies represent the first line of antigen‐specific immune defence protecting the mucosal surfaces against environmental pathogens and antigens and maintaining homoeostasis with the commensal microbiota. The polymeric Ig receptor (pIgR) plays the dual role of transporting locally produced dimeric IgA across mucosal epithelia and serving as the precursor of the secretory component moiety of SIgA. The complex regulation of pIgR expression and transcytosis by host and microbial factors is finely tuned to optimise the role of SIgA in mucosal immunity. Recent discoveries highlight the dynamic cross‐talk between pIgR, SIgA and the commensal microbiota that populate our mucosal surfaces. Dysregulation of pIgR expression and/or function can result in profound consequences for the pathogenesis of infectious, inflammatory and neoplastic diseases. Future research into the function and regulation of pIgR and SIgA may offer new insights into the prevention and treatment of diseases that originate at mucosal surfaces. Key Concepts: Secretory IgA (SIgA) antibodies represent the first line of antigen‐specific immune defence at mucosal surfaces. The polymeric immunoglobulin receptor (pIgR) transports dimeric IgA across mucosal epithelial cells and serves as the precursor for the secretory component of SIgA. Transcription of the PIGR gene in mucosal epithelial cells is regulated by signalling pathways initiated by host cytokines and microbial factors, involving the cytoplasmic adapter protein, myeloid differentiation primary response protein 88 (MyD88). SIgA mediates immune protection by immune exclusion, intracellular neutralisation of antigens and pathogens and excretion of IgA‐containing immune complexes by pIgR‐mediated epithelial transcytosis. Cross‐talk between pIgR, SIgA and commensal bacteria regulates the composition of the gut microbiota and promotes intestinal homoeostasis. Dysregulated expression or function of pIgR can contribute to the pathology of infectious, inflammatory and neoplastic diseases.

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A Rab11a-enriched subapical membrane compartment regulates a cytoskeleton-dependent transcytotic pathway in secretory epithelial cells of the lacrimal gland

Cited by 20 publications

References 43 publications

Internalization of adhesion junction proteins and their association with recycling endosome marker proteins in rat seminiferous epithelium

Internalization of adhesion junction proteins and their association with recycling endosome marker proteins in rat seminiferous epithelium

Polymeric immunoglobulin receptor traffics through two distinct apically targeted pathways in primary lacrimal gland acinar cells

The Polymeric Immunoglobulin Receptor

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