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Voltage-gated potassium (Kv) channels are involved in the proliferation and transformation of mammary epithelial cells. They are thought to be related to the development of breast carcinoma, although the exact role they play in this event remains unclear. In this study, we investigated whether the expression and function of Kv channels is associated with Caveolin-1 (Cav-1, a principal component of caveolae) in different cell lines. We found that expression of Cav-1 correlated with the expression of Kv channels in mammary epithelial cells (MCF10A, MCF10A-ST1, and MCF7), and silencing of Cav-1 inhibited the expression of KCNA5 (voltage-gated shaker-related subfamily A, member 5). Immunofluorescence analysis indicated the colocalization of KCNA5 with Cav-1, whereas immunoprecipitation suggested a possible interaction between the two proteins. Overall, our finding indicated that KCNA5 protein may interact with Cav-1, thereby contributing to the proliferation and early transformation of mammary cells. [ABSTRACT FROM AUTHOR]

Excitatory amino acid transporters EAAT1 (SLC1A3), EAAT2 (SLC1A2), EAAT3 (SLC1A1), and EAAT4 (SLC1A6) serve to clear L-glutamate from the synaptic cleft and are thus important for the limitation of neuronal excitation. EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. To this end cRNA encoding EAAT1, EAAT2, EAAT3, or EAAT4 was injected into Xenopus oocytes without or with additional injection of cRNA encoding caveolin-1. The L-glutamate (2 mM)-induced inward current (I Glu) was taken as a measure of glutamate transport. As a result, I Glu was observed in EAAT1-, EAAT2-, EAAT3-, or EAAT4-expressing oocytes but not in water-injected oocytes, and was significantly decreased by coexpression of caveolin-1. Caveolin-1 decreased significantly the maximal transport rate. Treatment of EAATs-expressing oocytes with brefeldin A (5 µM) was followed by a decrease in conductance, which was similar in oocytes expressing EAAT together with caveolin-1 as in oocytes expressing EAAT1-4 alone. Thus, caveolin-1 apparently does not accelerate transporter protein retrieval from the cell membrane. In conclusion, caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. [ABSTRACT FROM AUTHOR]