Rab3Gap1 mediates exocytosis of Claudin-1 and tight junction formation during epidermal barrier acquisition

Youssef, Gehad; Gerner, Lisa; Naeem, Aishath S.; Ralph, O; Ono, M.; O’Neill, CA; O'Shaughnessy, R

doi:10.1016/j.ydbio.2013.04.034

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…Barrier function is partially rescued in Ppp2r2a knockdown cells by Jun kinase (JNK) inhibition (2,4). Interaction between Cx43 and Zo-1 in rat epidermal keratinocytes, demonstrable by immunoprecipitation ( Fig.…”

Section: Ppp2r2a Dephosphorylates Cx43 Independent Of Cjun Dephosphormentioning

confidence: 97%

“…Akt induces expression of a protein phosphatase 2a (Pp2a) regulatory subunit, Ppp2r2a. Ppp2r2a knockdown prevents the tight junction protein Claudin-1 trafficking to the cell surface and causes paracellular barrier defects (2,4). Tight junctions are necessary for barrier function both in simple epithelia (5) and in the skin and prevent the paracellular transport of solutes and ions (5)(6)(7).…”

mentioning

confidence: 99%

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The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin‐43 dephosphorlyation during epidermal barrier acquisition

Gerner

Youssef²,

O'Shaughnessy³

2013

Experimental Dermatology

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Epidermal barrier acquisition during late mammalian development is a prerequisite for terrestrial existence. Over a 24-h period, the epidermis goes from being a barrier-deficient, dye permeable epithelium to a barrier-competent epithelium. We have previously shown that Akt signalling is necessary for barrier acquisition in the mouse and that the protein phosphatase 2A regulatory subunit Ppp2r2a causes barrier acquisition by dephosphorylation of cJun. Here, we demonstrate that there is transient interaction between the gap junction protein Connexin 43 (Cx43) and Zonula occludins-1 (Zo-1) during epidermal barrier acquisition. Ppp2r2a knockdown prevented plasma membrane co-localisation and interaction between the two proteins. Ppp2r2a knockdown also increased phosphorylation at Serine 368 of Connexin 43. Cx43 phosphorlyation at Serine368 occurred just prior to the interaction between Connexin 43 and Zo-1. We therefore propose a model in which Ppp2r2a is required both for the initial interaction between Zo-1 and Cx43 and the consequent dephosphorylation of Connexin 43, preventing interaction of Zo-1 and allowing Zo-1 to initiate tight junction formation and barrier acquisition.

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Section: Ppp2r2a Dephosphorylates Cx43 Independent Of Cjun Dephosphormentioning

confidence: 97%

mentioning

confidence: 99%

The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin‐43 dephosphorlyation during epidermal barrier acquisition

Gerner

Youssef²,

O'Shaughnessy³

2013

Experimental Dermatology

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“…Inhibiting claudin-1 exocytosis also causes a defect in epidermal barrier function (Fig. 4A; Youssef et al 2013). Significantly, the overall morphology and integrity of the epidermis in claudin-1 knock-out mice appeared normal, and other members of the claudin family were expressed.…”

Section: Epidermis Organization and Regulation Of Homeostasismentioning

confidence: 99%

Cell–Cell Junctions Organize Structural and Signaling Networks

García

Nelson

Chavez

2017

Cold Spring Harb Perspect Biol

341

253

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Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell proliferation and migration. Defects in cell-cell junctions give rise to a wide range of tissue abnormalities that disrupt homeostasis and are common in genetic abnormalities and cancers. Here, we discuss the organization and function of cell-cell junctions primarily involved in adhesion (Tight Junction, Adherens Junction, and Desmosomes) in two different epithelial tissues: a simple epithelium (intestine) and a stratified epithelium (epidermis). Studies in these tissues reveal similarities and differences in the organization and functions of different cell-cell junctions that meet the requirements for the specialized functions of each tissue. We discuss cell-cell junction responses to genetic and environmental perturbations that provide further insights into their roles in maintaining tissue homeostasis.

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“…In epithelial cells, the delivery of basolateral membrane proteins from the trans‐Golgi network (TGN) to the plasma membrane may be regulated at several steps, including vesicle delivery along microtubules (MTs), membrane tethering and fusion. Claudins are transported by exocytosis . Therefore, assembly of TJ may be regulated by these transport processes.…”

Section: Aj Provide a Platform For Traffickingmentioning

confidence: 99%

Cell Adhesion Structures in Epithelial Cells Are Formed in Dynamic and Cooperative Ways

Shigetomi

Ikenouchi

2019

BioEssays

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There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell-cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic changes in the organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. Figure 6. Addition of cholesterol restores the formation of TJ in α-catenin KO cells. Time-lapse imaging of α-catenin KO epithelial cells expressing GFP-claudin-3. Cholesterol-saturated MβCD (75 mM) was added to the medium to restore the level of cholesterol in the plasma membrane at time 0. GFP-claudin-3 gradually accumulate at the cell-cell interface and TJ is formed even in the absence of AJ. Scale bar, 20 µm. Adapted with permission. [72]

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Rab3Gap1 mediates exocytosis of Claudin-1 and tight junction formation during epidermal barrier acquisition

Cited by 13 publications

References 45 publications

The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin‐43 dephosphorlyation during epidermal barrier acquisition

The protein phosphatase 2A regulatory subunit Ppp2r2a is required for Connexin‐43 dephosphorlyation during epidermal barrier acquisition

Cell–Cell Junctions Organize Structural and Signaling Networks

Cell Adhesion Structures in Epithelial Cells Are Formed in Dynamic and Cooperative Ways

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