The RCC1 Domain of Protein Associated with Myc (PAM) Interacts with and Regulates KCC2

Garbarini, Nicole; Delpire, Eric

doi:10.1159/000149781

Cited by 40 publications

(40 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possibility is that tyrosine phosphorylation initiates carboxyl terminus interactions with accessory proteins involved in clustering or anchoring within lipid rafts. The yeast two-hybrid model identified protein associated with Myc (PAM) and brain-type creatine kinase (CKB) as KCC2 binding proteins (38,39), and KCC2 might interact with these or other unidentified proteins.…”

Section: Discussionmentioning

confidence: 99%

Clustering of Neuronal K+-Cl− Cotransporters in Lipid Rafts by Tyrosine Phosphorylation

Watanabe

Wake

Moorhouse

et al. 2009

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

] and hyperpolarizing GABAergic synaptic potentials. Depolarizing ␥-aminobutyric acid (GABA) responses in neonatal neurons and following various forms of neuronal injury are associated with reduced levels of KCC2 expression. Despite the importance for plasticity of inhibitory transmission, less is known about cellular mechanisms involved in more dynamic changes in KCC2 function. In this study, we investigated the role of tyrosine phosphorylation in KCC2 localization and function in hippocampal neurons and in cultured GT1-7 cells. Mutation to the putative tyrosine phosphorylation site within the long intracellular carboxyl terminus of KCC2(Y1087D) or application of the tyrosine kinase inhibitor genistein shifted the GABA reversal potential (E GABA ) to more depolarized values, indicating reduced KCC2 function. This was associated with a change in the expression pattern of KCC2 from a punctate distribution to a more uniform distribution, suggesting that functional tyrosine-phosphorylated KCC2 forms clusters in restricted membrane domains. Sodium vanadate, a tyrosine phosphatase inhibitor, increased the proportion of KCC2 associated with lipid rafts membrane domains. Loss of tyrosine phosphorylation also reduced oligomerization of KCC2. A loss of the punctuate distribution and oligomerization of KCC2 and a more depolarized E GABA were seen when the 28-amino-acid carboxyl terminus of KCC2 was deleted. These results indicate that direct tyrosine phosphorylation of KCC2 results in membrane clusters and functional transport activity, suggesting a mechanism by which intracellular Cl ؊ concentrations and GABA responses can be rapidly modulated. In addition to changes in the expression levels of KCC2 protein, the function of KCC2 can be more dynamically and rapidly modulated by the availability of transport substrates and by various forms of kinase activity. Cl Ϫ extrusion is quantitatively regulated by the K ϩ driving force across the membrane (8). Protein kinase C can down-regulate both KCC2 function (9) and surface expression (10). Staurosporine, a broad spectrum kinase inhibitor, produces a rapid up-regulation of KCC2 function in immature neurons (11). Brain-type creatinine kinase binding to KCC2 may also regulate its function (12). Finally, WNK3, by interacting with Ste20-related proline-alanine-rich kinase, prevents the cell swelling-induced activation of KCC2 in Xenopus oocytes (13,14).KCC2 contains one tyrosine protein kinase phosphorylation consensus site (Tyr-1087) within the long carboxyl terminus in the intracellular region (15). Tyr-1087 is not present in KCC1, another family of KCCs, suggesting that direct tyrosine phosphorylation may uniquely regulate KCC2. The receptor tyrosine kinase, IGF-1, and the soluble tyrosine kinase, Src kinase, activate KCC2 during maturation of hippocampal neurons (16). Oxidative stress decreases the tyrosine phosphorylation of KCC2 and reduces KCC2 function (17). However, just how tyrosine phosphorylation regulates KCC2 function under more physiological conditions is unclear, al...

show abstract

Section: Discussionmentioning

confidence: 99%

Clustering of Neuronal K+-Cl− Cotransporters in Lipid Rafts by Tyrosine Phosphorylation

Watanabe

Wake

Moorhouse

et al. 2009

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

show abstract

“…UV induces a variety of free radical and oxidative molecules, which because of their chemical reactivity alter the molecular structure and damage lipids, proteins and nucleic acids [79]. Antioxidant enzymes mediate the removal of ROS, with different enzymes functioning in specific compartments (e.g.…”

Section: Figurementioning

confidence: 99%

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

2014

View full text Add to dashboard Cite

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

show abstract

“…None of the β-carotene concentrations applied led to a plateau [18]. In human skin, the exposition to UV and IR radiation also induces a carotenoid reduction [32], [33], [34]. The cows subjected to the study were measured between January and early May, so that the cutaneous carotenoid concentration was not significantly affected by the varying influence of UV or IR radiation at the farms of origin.…”

Section: Discussionmentioning

confidence: 99%

Serial Non-Invasive Measurements of Dermal Carotenoid Concentrations in Dairy Cows following Recovery from Abomasal Displacement

et al. 2012

View full text Add to dashboard Cite

Maintaining the health of farm animals forms the basis for a sustainable and profitable production of food from animal origin. Recently, the effects of carotenoids on the oxidative status as well as on reproductive and immune functions in cattle have been demonstrated. The present study aimed at investigating dermal carotenoid levels in cattle recovering from abomasal displacement. For this purpose, serial in vivo measurements were undertaken using a miniaturized scanner system that relies on reflection spectroscopy (Opsolution GmbH, Kassel, Germany). In a first trial, repeated measurements of dermal carotenoid concentrations were performed on the udder skin of healthy non-lactating cattle (n = 6) for one month in weekly intervals. In a second trial, in vivo dermal carotenoid concentrations were determined in intervals in 23 cows following surgical treatment of abomasal displacement. The results show that dermal carotenoid concentrations, determined on a weekly basis over a period of one month, showed variations of up to 18% in the healthy individuals kept under constant conditions with respect to housing and nutrition. Repeated measurements during the recovery period following surgical treatment of abomasal displacement resulted in an increase in dermal carotenoid concentrations in 18 of 20 animals with a favourable outcome when compared with results obtained within 12 hours following surgery. The mean increase in dermal carotenoid concentrations in subsequent measurements was 53±44%, whereas levels decreased (mean 31±27%) in cattle with a fatal outcome.These results indicate potential applications for reflection spectroscopy for non-invasive early detection of changes in the dermal carotenoid concentrations as a reflection of the antioxidant status in an animal.

show abstract

The RCC1 Domain of Protein Associated with Myc (PAM) Interacts with and Regulates KCC2

Cited by 40 publications

References 88 publications

Clustering of Neuronal K+-Cl− Cotransporters in Lipid Rafts by Tyrosine Phosphorylation

Clustering of Neuronal K+-Cl− Cotransporters in Lipid Rafts by Tyrosine Phosphorylation

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

Serial Non-Invasive Measurements of Dermal Carotenoid Concentrations in Dairy Cows following Recovery from Abomasal Displacement

Contact Info

Product

Resources

About