Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene

Qiu, Min; Jiang, Lele; Matthaei, Klaus I.; Schoenwaelder, Simone M.; Kuffner, Támara; Mangin, P; Joseph, Joanne; Low, Joyce; Connor, David; Valenzuela, Stella M.; Curmi, Paul M. G.; Brown, Louise J.; Mahaut‐Smith, Martyn P.; Jackson, Shaun P.; Breit, Samuel N.

doi:10.1002/dvg.20590

Cited by 24 publications

(24 citation statements)

References 42 publications

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“…Platelets express the chloride intracellular channel 1 (CLIC1) which has a central punctate localization at rest, as expected for a vesicular distribution, but with some movement to the periphery upon exposure to ADP, which could indicate insertion into the plasma membrane upon activation [65]. CLIC1 has also been detected in a membrane proteomics screen [66].…”

Section: Organellar Ion Channelsmentioning

confidence: 99%

The unique contribution of ion channels to platelet and megakaryocyte function

Mahaut‐Smith

2012

Journal of Thrombosis and Haemostasis

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Summary. Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet‐dependent events. However, with the aid of transgenic mice and ‘surrogate’ patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP‐gated P2X1 channels, Orai1 store‐operated Ca2+ channels, voltage‐gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.

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Section: Organellar Ion Channelsmentioning

confidence: 99%

The unique contribution of ion channels to platelet and megakaryocyte function

Mahaut‐Smith

2012

Journal of Thrombosis and Haemostasis

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“…Most recently, the Breit group generated a CLIC1 knockout mouse and report platelet dysfunction as well as inhibited clotting in CLIC1 nullizygous mice [26]. There are no other gross phenotypes reported in the CLIC1 nullizygous mice.…”

Section: Introductionmentioning

confidence: 99%

Chloride intracellular channel 1 functions in endothelial cell growth and migration

Tung

Kitajewski

2010

J Angiogenesis Res

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BackgroundLittle is known about the role of CLIC1 in endothelium. These studies investigate CLIC1 as a regulator of angiogenesis by in vitro techniques that mimic individual steps in the angiogenic process.MethodsUsing shRNA against clic1, we determined the role of CLIC1 in primary human endothelial cell behavior.ResultsHere, we report that reduced CLIC1 expression caused a reduction in endothelial migration, cell growth, branching morphogenesis, capillary-like network formation, and capillary-like sprouting. FACS analysis showed that CLIC1 plays a role in regulating the cell surface expression of various integrins that function in angiogenesis including β1 and α3 subunits, as well as αVβ3 and αVβ5.ConclusionsTogether, these results indicate that CLIC1 is required for multiple steps of in vitro angiogenesis and plays a role in regulating integrin cell surface expression.

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“…This may also explain why anion channels have previously received much less attention than cation channels. It is worth noting that anion channels have been associated with cystic fibrosis, bleeding phenotypes, and inflammatory conditions [12, 13, 15, 26, 27] and may represent valuable therapeutic targets, as demonstrated by clinical use of CFTR modulators [28]. Further work will be required to investigate the contribution(s) by the cohort of platelet anion channels during platelet activation.…”

Section: Discussionmentioning

confidence: 99%

“…Proteomic [10] and transcriptomic [11] analyses have since identified numerous anion channels that may be expressed by platelets. Of these, functional expressions of CLIC1 (Intracellular Cl − channel-1) [12], TMEM16F [13], and pannexin-1 [14] have been confirmed. Indicative of a hemostatic role for anion channels, CLIC1- and TMEM16F-deficient mice have associated platelet-related bleeding phenotypes [12, 13].…”

Section: Introductionmentioning

confidence: 99%

“…Of these, functional expressions of CLIC1 (Intracellular Cl − channel-1) [12], TMEM16F [13], and pannexin-1 [14] have been confirmed. Indicative of a hemostatic role for anion channels, CLIC1- and TMEM16F-deficient mice have associated platelet-related bleeding phenotypes [12, 13]. Additionally, pannexin-1 channels have been shown to amplify platelet activation responses to threshold agonist concentrations [14].…”

Section: Introductionmentioning

confidence: 99%

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Extracellular chloride is required for efficient platelet aggregation

et al. 2017

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Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide. However, the rate of aggregation was substantially reduced in a manner that was dependent on the extracellular chloride concentration and aggregation in the absence of chloride was noticeably biphasic, indicative of impaired secondary signaling. This was further investigated by targeting secondary agonists with aspirin and apyrase or by blockade of the ADP receptor P2Y12. Under these conditions, the rates of aggregation were comparable to those recorded in the absence of extracellular chloride. Finally, we assessed platelet granule release by flow cytometry and report a chloride-dependent element of alpha, but not dense, granule secretion. Taken together these data support a role for anion channels in the efficient induction of platelet activation, likely via enhancement of secondary signaling pathways.

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Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene

Cited by 24 publications

References 42 publications

The unique contribution of ion channels to platelet and megakaryocyte function

The unique contribution of ion channels to platelet and megakaryocyte function

Chloride intracellular channel 1 functions in endothelial cell growth and migration

Extracellular chloride is required for efficient platelet aggregation

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