Differential effects of cholesterol and 7-dehydrocholesterol on ligand binding of solubilized hippocampal serotonin1A receptors: implications in SLOS

Chattopadhyay, Amitabha ; Paila, Yamuna Devi ; Jafurulla, Md. ; Chaudhuri, Arunima ; Singh, Pushpendra ; Murty, M. R. V. S. ; Vairamani, M. (2007) Differential effects of cholesterol and 7-dehydrocholesterol on ligand binding of solubilized hippocampal serotonin1A receptors: implications in SLOS Biochemical and Biophysical Research Communications, 363 (3). pp. 800-805. ISSN 0006-291X

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S00062...

Related URL: http://dx.doi.org/10.1016/j.bbrc.2007.09.040

Abstract

The serotonin1A receptor is an important member of the G-protein coupled receptor family, and is involved in the generation and modulation of a variety of cognitive, behavioral, and developmental functions. Solubilization of the hippocampal serotonin1A receptor by 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) is accompanied by loss of membrane cholesterol which results in a reduction in specific agonist binding activity. Replenishment of cholesterol to solubilized membranes restores the cholesterol content of the membrane and significantly enhances specific agonist binding activity. In order to test the stringency of the requirement of cholesterol in this process, we solubilized native hippocampal membranes followed by replenishment with 7-dehydrocholesterol (7-DHC). 7-DHC is an immediate biosynthetic precursor of cholesterol differing only in a double bond at the 7th position in its sterol ring. Our results show, for the first time, that replenishment of solubilized hippocampal membranes with 7-DHC does not restore ligand binding activity of the serotonin1A receptor, in spite of recovery of the overall membrane order. This observation shows that the requirement for restoration of ligand binding activity is more stringent than the requirement for the recovery of overall membrane order. These novel results have potential implications in understanding the interaction of membrane sterols with this important neuronal receptor under pathogenic conditions such as the Smith-Lemli-Opitz syndrome.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Serotonin1A Receptor; Cholesterol; 7-dehydrocholesterol; Solubilization; Smith-lemli-opitz Syndrome; Ligand Binding Activity
ID Code:7089
Deposited On:25 Oct 2010 12:37
Last Modified:16 May 2016 17:20

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