| Autor: |
Tumova, S., Hou, B., Amer, M. S., McKeown, L., Moss, N. K., Bahnasi, Y. M., Li, J., Porter, K. E., Sivaprasadarao, A., Beech, D. J. |
| Předmět: |
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| Zdroj: |
Proceedings of the Physiological Society; 2013, p410P-410P, 1/3p |
| Abstrakt: |
The channels from the Transient Receptor Potential Canonical (TRPC) family are highly relevant in physiological or patho-physiological calcium signalling, especially in cardiovascular, neural or adipose tissue. TRPC5 channel is one of the family members which can function as a homotetramer or in a heteromultimeric assembly with other TRPC channels including TRPC1 (Sukumar et al, 2012). We studied the channels in human vascular smooth muscle cells obtained with ethical approval and in human embryonic kidney cell line exogeneously expressing TRPC5 alone or in combination with TRPC1. We find that cholesterol causes TRPC5 homomer internalization via caveolin-1-dependent retraction, as evidenced by immunostaining, cell surface TRPC5 quantification and calcium influx measurement. On the other hand, lipid raft analysis and GM1 co-localization indicate that heteromultimerization with TRPC1 changes TRPC5 localization in plasma membrane microdomains and this prevents the cholesterol-triggered retraction. Thus, besides affecting the selectivity or gating mechanism of the channel assembly, introduction of TRPC1 has additional functional impact by modifying the membrane localization of the channel. Our study suggests this would be especially pronounced in the face of increased, patho-physiological cholesterol levels. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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