Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization

Etienne-Manneville, Sandrine; Manneville, Jean‐Baptiste; Nicholls, Sarah; Ferenczi, Michael A.; Hall, Alan

doi:10.1083/jcb.200412172

Cited by 280 publications

(304 citation statements)

References 25 publications

Supporting

Mentioning

290

Contrasting

Unclassified

Order By: Relevance

“…Here, we show that PKCi has a role in promoting glioblastoma cell invasion. There is a precedent from the previous studies showing that atypical protein kinase C is involved in the polarized migration of cultured astrocytes (Etienne-Manneville et al, 2005) and that PKCi is involved in the nicotine-activated migration and invasion of H1299 human non-small cell lung cancer cells (Xu and Deng, 2006). The actin cytoskeleton is a dynamic element within cells that undergoes changes that are essential to cell motility (Lambrechts et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Regulation of glioblastoma cell invasion by PKCι and RhoB

Baldwin

Parolin²,

Lorimer

2008

Oncogene

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Regulation of glioblastoma cell invasion by PKCι and RhoB

Baldwin

Parolin²,

Lorimer

2008

Oncogene

View full text Add to dashboard Cite

“…These results indicated that in CTLs, similarly to T H cells (14), the PKCζ pathway is active at the IS. We thus treated CTLs with a selective pseudosubstrate inhibitor of PKCζ (PKCζ-PS) (16) to investigate the impact of PKCζ signaling blockade on MTOC polarization. PKCζ-PS treatment did not affect CTL viability (Fig.…”

Section: Resultsmentioning

confidence: 99%

An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse

Bertrand

Müller

Roh

et al. 2013

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

105

View full text Add to dashboard Cite

It is presently assumed that lethal hit delivery by cytotoxic T lymphocytes (CTLs) is mechanistically linked to centrosome polarization toward target cells, leading to dedicated release of lytic granules within a confined secretory domain. Here we provide three lines of evidence showing that this mechanism might not apply as a general paradigm for lethal hit delivery. First, in CTLs stimulated with immobilized peptide-MHC complexes, lytic granules and microtubule organizing center localization into synaptic areas are spatio-temporally dissociated, as detected by total internal reflection fluorescence microscopy. Second, in many CTL/target cell conjugates, lytic granule secretion precedes microtubule polarization and can be detected during the first minute after cell-cell contact. Third, inhibition of microtubule organizing center and centrosome polarization impairs neither lytic granule release at the CTL synapse nor killing efficiency. Our results broaden current views of CTL biology by revealing an extremely rapid step of lytic granule secretion and by showing that microtubule organizing center polarization is dispensable for efficient lethal hit delivery.immunological synapse | T-cell antigen receptor | protein kinase Cζ | signal transduction

show abstract

“…3) suggests that Dlgh1 might function cellautonomously, perhaps by either clustering signaling receptors in SMCs (10) or regulating their orientation via effects on the cytoskeleton, as shown in astrocytes (28). The generation of ureteric epithelium-and SMC-specific mutations in Dlgh1, using a conditional Dlgh1 allele and appropriate Cre transgenes, will allow us to address these issues.…”

Section: Discussionmentioning

confidence: 99%

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Mahoney¹,

Sammut

Xavier

et al. 2006

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

View full text Add to dashboard Cite

Discs-large homolog 1 (DLGH1) is a mouse ortholog of the Drosophila discs-large (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein families. DLG proteins play important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function. Here, we generated a null allele of Dlgh1 and studied its role in urogenital development. Dlgh1 ؊/؊ mice developed severe urinary tract abnormalities, including congenital hydronephrosis, which is the leading cause of renal failure in infants and children. DLGH1 is expressed in the developing ureter; in its absence, the stromal cells that normally lie between the urothelial and smooth muscle layers were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle cells were misaligned in a longitudinal orientation. These abnormalities in the ureter led to severely impaired ureteric peristalsis. Similar smooth muscle defects are observed frequently in patients with ureteropelvic junction obstruction, a common form of hydronephrosis. Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis.SAP97 ͉ kidney ͉ postsynaptic density-95/discs-large/zonula occludens-1 ͉ urogenital ͉ sonic hedgehog

show abstract

Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization

Cited by 280 publications

References 25 publications

Regulation of glioblastoma cell invasion by PKCι and RhoB

Regulation of glioblastoma cell invasion by PKCι and RhoB

An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Contact Info

Product

Resources

About