Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane

Deutsch, Emily; Weigel, Aubrey V.; Akin, Elizabeth J.; Fox, Philip D.; Hansen, Gentry; Haberkorn, Christopher J.; Loftus, Rob J.; Krapf, Diego; Tamkun, Michael M.

doi:10.1091/mbc.e12-01-0047

Cited by 94 publications

(106 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, there is a growing list of ion channels that possess functions unrelated to ion conduction (Kaczmarek, 2006). Consistent with this idea, we have recently discovered that in both HEK 293 cells and hippocampal neurons, multiple membrane proteins are preferentially trafficked to and from the plasma membrane at the perimeter of Kv2.1 clusters, suggesting the clusters define cell surface trafficking hubs (Deutsch et al, 2012).…”

Section: Introductionmentioning

confidence: 57%

“…The finding that RyRs are often adjacent to Kv2.1 on the neuronal soma (Mandikian et al, 2014) further supports this idea. Given that endo-and exocytosis often occur adjacent to the Kv2.1 cluster perimeter (Deutsch et al, 2012), these domains might also link Ca 2+ signaling to membrane trafficking in both the neuronal soma and axon initial segment.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of non-conducting Kv2.1 channels (Fox et al, 2013b;O'Connell et al, 2010) allows the clusters to achieve the high channel density that is required to induce junction formation without compromising electrical signaling. Given the well-accepted role of ER-plasmamembrane junctions in Ca 2+ homeostasis in immune cells (Hogan et al, 2010) and that Kv2.1 clusters serve as sites for endo-and exocytosis (Deutsch et al, 2012), the Kv2.1-induced ER-plasmamembrane junctions are proposed to represent a macromolecular complex that functions as a scaffolding site to couple membrane trafficking to Ca 2+ signaling.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Fox

Haberkorn

Akin

et al. 2015

Journal of Cell Science

Self Cite

107

158

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Fox

Haberkorn

Akin

et al. 2015

Journal of Cell Science

Self Cite

107

158

View full text Add to dashboard Cite

show abstract

“…Although the clustered channels may conduct current poorly (70), these aggregates appear to be the site of surface delivery of additional Kv2.1 protein (71). Therefore, it will be important to establish in future work whether stimuli that affect channel clustering (72,73) can regulate the SNARE-dependent insertion of new channels during apoptosis, as was evaluated for a stromal cell-derived chemokine (26).…”

Section: Discussionmentioning

confidence: 99%

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

McCord

Aizenman

2013

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

View full text Add to dashboard Cite

A simultaneous increase in cytosolic Zn 2+ and Ca 2+ accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca 2+ -dependent activation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn 2+ . We have reported that oxidant-induced intraneuronal Zn 2+ liberation triggers a syntaxin-dependent incorporation of Kv2.1 voltage-gated potassium channels into the plasma membrane. This channel insertion can be detected as a marked enhancement of delayed rectifier K + currents in voltage clamp measurements observed at least 3 h following a short exposure to an apoptogenic stimulus. This current increase is the process responsible for the cytoplasmic loss of K + that enables protease and nuclease activation during apoptosis. In the present study, we demonstrate that an oxidative stimulus also promotes intracellular Ca 2+ release and activation of CaMKII, which, in turn, modulates the ability of syntaxin to interact with Kv2.1. Pharmacological or molecular inhibition of CaMKII prevents the K + current enhancement observed following oxidative injury and, importantly, significantly increases neuronal viability. These findings reveal a previously unrecognized cooperative convergence of Ca 2+ -and Zn 2+ -mediated injurious signaling pathways, providing a potentially unique target for therapeutic intervention in neurodegenerative conditions associated with oxidative stress.

show abstract

“…In a TIRF assay, when a molecule is internalized it leaves the excitation evanescent field. So the termination of a QD trajectory is indicative of an endocytic event (20,21). QDs are particularly suitable for these measurements because they do not display photobleaching.…”

Section: Significancementioning

confidence: 99%

Quantifying the dynamic interactions between a clathrin-coated pit and cargo molecules

Weigel¹,

Tamkun²,

Krapf

2013

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

Self Cite

View full text Add to dashboard Cite

Clathrin-mediated endocytosis takes place through the recruitment of cargo molecules into a growing clathrin-coated pit (CCP). Despite the importance of this process to all mammalian cells, little is yet known about the interaction dynamics between cargo and CCPs. These interactions are difficult to study because CCPs display a large degree of lifetime heterogeneity and the interactions with cargo molecules are time dependent. We use single-molecule total internal reflection fluorescence microscopy, in combination with automatic detection and tracking algorithms, to directly visualize the recruitment of individual voltage-gated potassium channels into forming CCPs in living cells. We observe association and dissociation of individual channels with a CCP and, occasionally, their internalization. Contrary to widespread ideas, cargo often escapes from a pit before abortive CCP termination or endocytic vesicle production. Thus, the binding times of cargo molecules associating to CCPs are much shorter than the overall endocytic process. By measuring tens of thousands of capturing events, we build the distribution of capture times and the times that cargo remains confined to a CCP. An analytical stochastic model is developed and compared with the measured distributions. Due to the dynamic nature of the pit, the model is non-Markovian and it displays long-tail power law statistics. The measured distributions and model predictions are in excellent agreement over more than five orders of magnitude. Our findings identify one source of the large heterogeneities in CCP dynamics and provide a mechanism for the anomalous diffusion of proteins in the plasma membrane.single-molecule tracking | Levy statistics | live-cell imaging | TIRF

show abstract

Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane

Cited by 94 publications

References 63 publications

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

Quantifying the dynamic interactions between a clathrin-coated pit and cargo molecules

Contact Info

Product

Resources

About

Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane

Cited by 94 publications

References 63 publications

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Convergent Ca 2+ and Zn 2+ signaling regulates apoptotic Kv2.1 K + currents

Quantifying the dynamic interactions between a clathrin-coated pit and cargo molecules

Contact Info

Product

Resources

About

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents