MARK2/EMK1/Par-1Bα Phosphorylation of Rab11-Family Interacting Protein 2 Is Necessary for the Timely Establishment of Polarity in Madin-Darby Canine Kidney Cells

Ducharme, Nicole A.; Hales, Chadwick M.; Lapierre, Lynne A.; Ham, Amy-Joan L.; Oztan, Asli; Apodaca, Gerard; Goldenring, James R.

doi:10.1091/mbc.e05-08-0736

Cited by 57 publications

(74 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These apical trafficking programs are controlled by Rab11a, which recruits and activates Rab8a on subapical vesicles via the Rab GEF, Rabin8 (10). In addition, phosphorylation by Par1b of Rab11-FIP2, which binds to both Rab11a and Myo5B, is necessary for proper establishment of polarity in Madine-Darby canine kidney (MDCK) cells (11). The cooperation of Rab8a and Rab11a in apical trafficking supports the hypothesis that association with both GTPases may regulate Myo5B participation in apical membrane transport.…”

mentioning

confidence: 65%

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Roland

Bryant

Datta

et al. 2011

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

Self Cite

175

201

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 65%

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Roland

Bryant

Datta

et al. 2011

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

Self Cite

175

201

View full text Add to dashboard Cite

show abstract

“…Next, knockdown experiments were conducted in MCF10A cells to determine whether RNF41, like Par-1b, is required for epithelial cell polarity (Böhm et al, 1997;Cohen et al, 2007;Cox et al, 2001a;Doerflinger et al, 2003;Ducharme et al, 2006). MCF10A is a spontaneously immortalized but untransformed mammary epithelial cell line.…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of RNF41 E3 ubiquitin ligase by Par-1 protein kinase required for epithelial cell polarity

Lewandowski

Piwnica‐Worms

2013

Journal of Cell Science

View full text Add to dashboard Cite

The establishment and maintenance of cell polarity is an essential property governing organismal homeostasis, and loss of polarity is a common feature of cancer cells. The ability of epithelial cells to establish apical-basal polarity depends on intracellular signals generated from polarity proteins, such as the Par-1 family of proteins, as well as extracellular signals generated through cell contacts with the extracellular matrix (ECM). The Par-1 family has a well-established role in regulating cell-cell contacts in the form of tight junctions by phosphorylating Par-3. In addition, Par-1 has been shown to impact on cell-ECM interactions by regulating laminin receptor localization and laminin deposition on the basal surface of epithelial cells. Laminins are major structural and signaling components of basement membrane (BM), a sheet of specialized ECM underlying epithelia. In this study, we identify RNF41, an E3 ubiquitin ligase, as a novel Par-1b (also known as MARK2) effector in the cell-ECM pathway. Par-1b binds to and phosphorylates RNF41 on serine 254. Phosphorylation of RNF41 by Par-1b is required for epithelial cells to localize laminin-111 receptors to their basolateral surfaces and to properly anchor to laminin-111. In addition, phosphorylation of RNF41 is required for epithelial cells to establish apical-basal polarity. Our data suggests that phosphorylation of RNF41 by Par-1b regulates basolateral membrane targeting of laminin-111 receptors, thereby facilitating cell anchorage to laminin-111 and ultimately forming the cell-ECM contacts required for epithelial cells to establish apical-basal cell polarity.

show abstract

“…However, few studies have directly addressed the role of Rab proteins in epithelial neoplasia. Nevertheless, investigations over the past several years have increasingly pointed to roles for Rab proteins and their effectors in the regulation of aspects of the establishment and maintenance of polarity (27). The loss of polarity in epithelial cells represents a critical early event in the pathway toward neoplastic transformation (28).…”

Section: Discussionmentioning

confidence: 99%

Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas

Nam¹,

Lee²,

Smith³

et al. 2010

J. Clin. Invest.

Self Cite

134

137

View full text Add to dashboard Cite

MARK2/EMK1/Par-1Bα Phosphorylation of Rab11-Family Interacting Protein 2 Is Necessary for the Timely Establishment of Polarity in Madin-Darby Canine Kidney Cells

Cited by 57 publications

References 59 publications

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization

Phosphorylation of RNF41 E3 ubiquitin ligase by Par-1 protein kinase required for epithelial cell polarity

Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas

Contact Info

Product

Resources

About