The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity

Tzaban, Salit; Massol, Ramiro; Yen, Elizabeth H.; Hamman, Wendy; Frank, Scott R.; Lapierre, Lynne A.; Hansen, Steen Ingemann; Goldenring, James R.; Blumberg, Richard S.; Lencer, Wayne I.

doi:10.1083/jcb.200809122

Cited by 151 publications

(155 citation statements)

References 62 publications

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“…Myo5B can also associate with Rab25 through the same binding site used by Rab11a (6). Recent investigations indicate that Rab25 regulates apical to basal transcytosis (24) and 3D cyst lumen formation (10) (25). Thus, the contribution of Rab25-Myo5B interactions to epithelial polarization remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Roland

Bryant

Datta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The Rab GTPases are the largest family of proteins regulating membrane traffic. Rab proteins form a nidus for the assembly of multiprotein complexes on distinct vesicle membranes to regulate particular membrane trafficking pathways. Recent investigations have demonstrated that Myosin Vb (Myo5B) is an effector for Rab8a, Rab10, and Rab11a, all of which are implicated in regulating different pathways for recycling of proteins to the plasma membrane. It remains unclear how specific interactions of Myo5B with individual Rab proteins can lead to specificity in the regulation of alternate trafficking pathways. We examined the relative contributions of Rab/Myo5B interactions with specific pathways using Myo5B mutants lacking binding to either Rab11a or Rab8a. Myo5B Q1300L and Y1307C mutations abolished Rab8a association, whereas Myo5B Y1714E and Q1748R mutations uncoupled association with Rab11a. Expression of Myo5B tails containing these mutants demonstrated that Rab11a, but not Rab8a, was required for recycling of transferrin in nonpolarized cells. In contrast, in polarized epithelial cyst cultures, Myo5B was required for apical membrane trafficking and de novo lumen formation, dependent on association with both Rab8a and Rab11a. These data demonstrate that different combinations of Rab GTPase association with Myo5B control distinct membrane trafficking pathways.

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Section: Discussionmentioning

confidence: 99%

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Roland

Bryant

Datta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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181

201

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“…31,32 and has previously been associated with defective MDCK cyst lumen formation. 29 Inactivation of Rab25 or the related Rab11a resulted in a multiple lumen phenotype in epithelial cysts, which is characterized by failure of lumen expansion and retention of podocalyxin in subapical vesicles.…”

Section: Discussionmentioning

confidence: 99%

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Aue

Hinze

Walentin

et al. 2015

Journal of the American Society of Nephrology

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Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia. The renal collecting duct's vital electrolyte and waterregulatory functions are carried out by highly specialized cell populations. 1 The collecting duct itself is composed of a tight epithelium, which separates the urinary compartment from a hypertonic interstitium and maintains a barrier to concentration gradients. The collecting duct derives from the ureteric bud, which emanates from the nephric duct and then undergoes branching morphogenesis in response to signals from the adjacent metanephric mesenchyme. 2 Many of the genes that are critical for aspects of nephric duct development continue to be expressed in the ureteric bud and collecting duct, serving roles in development, differentiation, and maintenance of these cells (e.g., Pax2/8, Gata3, Emx2, and Hnf1b). 3 Little is known about the molecular pathways governing the specific epithelial properties of these cells, although it is clear that these epithelia share several cell biologic properties such as a uniform tubular appearance characterized by a cuboidal epithelium surrounding a fluid-filled lumen and a molecular composition of the apical junctional complex that includes

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“…Other regulators of transport included Rab 25 and myosin Vb in transcytosis, Rab11a in basolateral recycling and exocytosis, and Rab 7 in lysosome targeting. 4,23 In dendritic cells, FcRn was found to mediate the transport of multimeric IgG-antigen complex (multiple IgGs attached to a single antigen) to the lysosome, but not that of monomeric IgG-antigen complex (antigen with a single IgG).…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…FcRn is also known to mediate bidirectional transcytosis of IgG across epithelial cells as well as membrane recycling. 3,4 FcRn-IgG interaction also functions in antigen presentation and cross-presentation in macrophage and dendritic cells. 5,6 Each of these functions has important implications in therapeutic antibody development.…”

Section: Fundamental Biology Of Fcrnmentioning

confidence: 99%

Neonatal Fc receptor and IgG-based therapeutics

Kuo

Aveson²

2011

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206

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The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity

Cited by 151 publications

References 62 publications

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion

Neonatal Fc receptor and IgG-based therapeutics

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