Faculty Opinions recommendation of Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling.

Dishevelled-Associating Protein with a high frequency of LEucines (DAPLE) belongs to a group of unconventional activators of heterotrimeric G-proteins that are cytoplasmic factors rather than membrane proteins of the G-protein–coupled receptor superfamily. During neurulation, DAPLE localizes to apical junctions of neuroepithelial cells and promotes apical cell constriction via G-protein activation. While junctional localization of DAPLE is necessary for this function, the factors it associates with at apical junctions or how they contribute to DAPLE-mediated apical constriction are unknown. MPDZ is a multi-PDZ (PSD95/DLG1/ZO-1) domain scaffold present at apical cell junctions whose mutation in humans is linked to nonsyndromic congenital hydrocephalus (NSCH). DAPLE contains a PDZ-binding motif (PBM) and is also mutated in human NSCH, so we investigated the functional relationship between both proteins. DAPLE colocalized with MPDZ at apical cell junctions and bound directly to the PDZ3 domain of MPDZ via its PBM. Much like DAPLE, MPDZ is induced during neurulation in Xenopus and is required for apical constriction of neuroepithelial cells and subsequent neural plate bending. MPDZ depletion also blunted DAPLE-mediated apical constriction of cultured cells. These results show that DAPLE and MPDZ, two factors genetically linked to NSCH, function as cooperative partners at apical junctions and are required for proper tissue remodeling during early stages of neurodevelopment.

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Localization and Regulation of Claudin-14 in Experimental Models of Hypercalcemia

AJP Renal Physiology ◽

10.1152/ajprenal.00397.2020 ◽

2020 ◽

Author(s):

Sebastian Frische ◽

R. Todd Alexander ◽

Patrícia Ferreira ◽

Rebecca Tan ◽

Weidong Wang ◽

...

Keyword(s):

Cellular Localization ◽

Stone Formation ◽

Apical Cell ◽

Experimental Models ◽

Cell Junctions ◽

Cell Periphery ◽

Increased Risk ◽

Junction Protein ◽

Lacz Activity ◽

Kidney Stone Formation

Variations in the CLDN14 gene have been linked to increased risk of hypercalciuria and kidney stone formation. However, the exact cellular localization of CLDN14 and its regulation remain to be fully delineated. To this end, we generated a novel antibody that allowed the detection of CLDN14 in paraffin-embedded renal sections. This showed CLDN14 to be detectable in the kidney only after induction of hypercalcemia in rodent models. Protein expression in kidney is localized exclusively to the thick ascending limbs (TAL), mainly restricted to the cortical and upper medullary portion of the kidney. However not all cells in the TAL expressed the tight junction protein. In fact, CLDN14 was primarily expressed in cells also expressing CLDN16, but devoid of CLDN10. CLDN14 appeared in very superficial apical cell domains and near cell junctions in a belt-like formation along the apical cell periphery. In transgenic mice, Cldn14 promotor-driven LacZ activity did not show complete colocalization with CLDN14 protein nor was it increased by hypercalcemia, suggesting that LacZ activity cannot be used as a marker for CLDN14 localization and regulation in this model. In conclusion, CLDN14, showed a restricted localization pattern in the apical domain of select cells of the TAL.

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Faculty Opinions recommendation of NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717998091.793481691 ◽

2013 ◽

Author(s):

Alan Fanning ◽

Laurel Rodgers

Keyword(s):

Apical Cell ◽

Cell Junctions ◽

Tissue Geometry

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Increased levels of the Drosophila Abelson tyrosine kinase in nerves and muscles: subcellular localization and mutant phenotypes imply a role in cell-cell interactions

Development ◽

10.1242/dev.116.4.953 ◽

1992 ◽

Vol 116 (4) ◽

pp. 953-966 ◽

Cited By ~ 3

Author(s):

R.L. Bennett ◽

F.M. Hoffmann

Keyword(s):

Nervous System ◽

Tyrosine Kinase ◽

Expression Patterns ◽

Apical Cell ◽

Cell Interactions ◽

Cell Junctions ◽

Imaginal Disk ◽

Abelson Tyrosine Kinase ◽

Mutant Phenotypes ◽

Cell Cell

Mutations in the Drosophila Abelson tyrosine kinase have pleiotropic effects late in development that lead to pupal lethality or adults with a reduced life span, reduced fecundity and rough eyes. We have examined the expression of the abl protein throughout embryonic and pupal development and analyzed mutant phenotypes in some of the tissues expressing abl. abl protein, present in all cells of the early embryo as the product of maternally contributed mRNA, transiently localizes to the region below the plasma membrane cleavage furrows as cellularization initiates. The function of this expression is not yet known. Zygotic expression of abl is first detected in the post-mitotic cells of the developing muscles and nervous system midway through embryogenesis. In later larval and pupal stages, abl protein levels are also highest in differentiating muscle and neural tissue including the photoreceptor cells of the eye. abl protein is localized subcellularly to the axons of the central nervous system, the embryonic somatic muscle attachment sites and the apical cell junctions of the imaginal disk epithelium. Evidence for abl function was obtained by analysis of mutant phenotypes in the embryonic somatic muscles and the eye imaginal disk. The expression patterns and mutant phenotypes indicate a role for abl in establishing and maintaining cell-cell interactions.

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Planar cell polarization requires Widerborst, a B′ regulatory subunit of protein phosphatase 2A

Development ◽

10.1242/dev.129.14.3493 ◽

2002 ◽

Vol 129 (14) ◽

pp. 3493-3503 ◽

Cited By ~ 2

Author(s):

Michael Hannus ◽

Fabian Feiguin ◽

Carl-Philipp Heisenberg ◽

Suzanne Eaton

Keyword(s):

Apical Cell ◽

Cell Polarization ◽

Cell Junctions ◽

Regulatory Subunit ◽

Convergent Extension ◽

Tissue Polarity ◽

Wing Hair ◽

Distal Side ◽

Phosphatase 2A ◽

Pp2a Activation

We have identified widerborst (wdb), a B′ regulatory subunit of PP2A, as a conserved component of planar cell polarization mechanisms in both Drosophila and in zebrafish. In Drosophila, wdb acts at two steps during planar polarization of wing epithelial cells. It is required to organize tissue polarity proteins into proximal and distal cortical domains, thus determining wing hair orientation. It is also needed to generate the polarized membrane outgrowth that becomes the wing hair. Widerborst activates the catalytic subunit of PP2A and localizes to the distal side of a planar microtubule web that lies at the level of apical cell junctions. This suggests that polarized PP2A activation along the planar microtubule web is important for planar polarization. In zebrafish, two wdb homologs are required for convergent extension during gastrulation, supporting the conjecture that Drosophila planar cell polarization and vertebrate gastrulation movements are regulated by similar mechanisms.

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