Insulin receptors and luteinizing hormone receptors (LHR), as examples, accumulate in membrane microdomains in response to binding of their respective ligands. We have previously compared the effects of insulin and bis(maltolato)oxovanadium(IV) (BMOV) on the distribution of insulin receptors within plasma membrane microdomains. BMOV appears to indirectly activate insulin receptors by decreasing cell-surface membrane order thus increasing the likelihood that insulin receptors are retained in detergent-resistant membrane microdomains where they are more readily phosphorylated. The question raised by these results is whether receptor numbers in the plasma membrane, together with BMOV, can affect receptor signaling in the absence of ligand, particularly when receptor numbers per cell are large. We have used polarized homo-transfer fluorescence resonance energy transfer to evaluate the oligerimerization of LHR when cells stably express &lt;7,000 receptors per cell, 8,000-30,000 receptors per cell, 35,000-80,000 receptors per cell or &gt;85,000 receptors per cell. At lower receptor numbers per cell, it is likely that LHRs appear in membranes as receptor monomers or small clusters of receptors. At higher receptor numbers per cell, receptors appear in significantly larger clusters. Flow cytometric analysis of cyclic adenosine monophosphate (cAMP) levels per cell indicate that extensively clustered LHR which are associated with membrane microdomains are also constitutively active and unlikely to be further activated by binding of hormone. The effects of BMOV on hormone-mediated signaling through aggregation of LHR in large clusters will also be discussed.

Bis(maltolato)oxovanadium(IV) effects on luteinizing hormone receptor signal transduction

2019 Spring National Meeting

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