Evidence for a Functional Interaction between the ClC-2 Chloride Channel and the Retrograde Motor Dynein Complex

Dhani, Sonja; Mohammad-Panah, Raha; Ahmed, Najma N.; Ackerley, Cameron; Ramjeesingh, Mohabir; Bear, Christine E.

doi:10.1074/jbc.m209828200

Cited by 40 publications

(46 citation statements)

References 45 publications

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“…The distribution of ClC-2-GFP protein in transiently transfected HEK-293 cells is similar to that seen by immunofluorescence in COS7 fibroblasts, which express ClC-2 endogenously. The distribution in COS7 cells was seen to correspond to plasma membrane, early endosome, and perinuclear localization (8). This type of distribution is consistent with the results observed here.…”

Section: Discussionsupporting

confidence: 82%

Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies

Niemeyer

Yusef

Cornejo

et al. 2004

Physiological Genomics

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Section: Discussionsupporting

confidence: 82%

Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies

Niemeyer

Yusef

Cornejo

et al. 2004

Physiological Genomics

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“…To find out whether the dynein motor was involved, we first resorted to EHNA, a known inhibitor of the dynein ATPase activity (11,12). As a control, we first confirmed that EHNA caused dispersal of giantin in the Golgi apparatus, 2 the aggregation of which being a known dynein-dependent process (13,14).…”

Section: Mkk6 Directly Associates With Tubulin-as P150mentioning

confidence: 78%

p150Glued, Dynein, and Microtubules Are Specifically Required for Activation of MKK3/6 and p38 MAPKs

Cheung

Zhang

Long

et al. 2004

Journal of Biological Chemistry

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To look for regulators of the mitogen-activated protein kinase (MAPK) kinase 6 (MKK6), a yeast two-hybrid screen was initiated using MKK6 as bait. p150Glued dynactin, a key component of the cytoplasmic dynein-dynactin motor complex, was found to specifically interact with MKK6 and its close homologue MKK3. Silencing of p150Glued expression by small interference RNA reduced the stimulus-induced phosphorylation of MKK3/6 and p38 MAPKs. The similar adverse effect was also seen when the cytoplasmic dynein motor was disrupted by other means. Like p150Glued , MKK3/6 directly associate with microtubules. Disruption of microtubules prior to cell stimulation specifically inhibits the stimulus-induced phosphorylation of both MKK3/6 and p38 MAPKs. Our unexpected findings reveal a specific requirement for p150Glued /dynein/functional microtubules in activation of MKK3/6 and p38 MAPKs in vivo.

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“…A recent study, for example, determined that ␤-tubulin binds to the TRP channel vanilloid receptor (TRPV1) in a Ca 2ϩ -dependent manner (36). More interestingly, however, is the fact that at least another channel is associated with dynein motor proteins, a phenomenon also associated with the specificity of cell targeting of the ClC-2 channel (37).…”

Section: Discussionmentioning

confidence: 99%

Polycystin-2 Cation Channel Function Is under the Control of Microtubular Structures in Primary Cilia of Renal Epithelial Cells

Montalbetti

et al. 2006

Journal of Biological Chemistry

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Mutations in the gene encoding polycystin-2 (PC2) result in autosomal dominant polycystic kidney disease and defects in left-right asymmetry during embryogenesis. PC2 is a TRP-type Ca 2؉ -permeable non-selective cation channel, which is expressed in kidney and other organs. PC2 is present and functional in microtubule-containing primary cilia of renal epithelial cells. However, no information is yet available as to whether PC2 interacts with microtubules. Here, we assessed the role of microtubular dynamics in regulating PC2 channel function in primary cilia. Isolated ciliary membranes from LLC-PK1 epithelial cells were reconstituted in a lipid bilayer system. The acute addition of the microtubular disrupter colchicine (15 M) rapidly abolished, whereas the addition of the microtubular stabilizer paclitaxel (taxol, 15 M) increased ciliary PC2 channel activity. The further addition of ␣-tubulin plus GTP also stimulated PC2 channel activity in ciliary membranes. However, ␣-tubulin and GTP had no effect on in vitro translated PC2. Using the yeast two-hybrid assay, we found that PC2 interacts with the microtubule-dependent motor kinesin-2 subunit KIF3A, a protein involved in polycystic kidney disease. The interaction occurred through the carboxyl termini domain of both proteins, which was further confirmed by in vitro glutathione S-transferase pull-down and dot blot overlay assays. Co-immunoprecipitation experiments showed that PC2 and KIF3A are in the same complex in native HEK293, Madin-Darby canine kidney cells (MDCK), and LLC-PK1 cells. Immunofluorescent staining also showed substantial PC2 and KIF3A co-localization in primary cilia of renal epithelial cells. The data indicate that microtubular organization regulates PC2 function, which may explain, among others, the regulatory role of PC2 in the sensory function of primary cilia.

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Evidence for a Functional Interaction between the ClC-2 Chloride Channel and the Retrograde Motor Dynein Complex

Cited by 40 publications

References 45 publications

Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies

Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies

p150Glued, Dynein, and Microtubules Are Specifically Required for Activation of MKK3/6 and p38 MAPKs

Polycystin-2 Cation Channel Function Is under the Control of Microtubular Structures in Primary Cilia of Renal Epithelial Cells

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