ABSTRACT
Soluble adenylyl cyclase (sAC) represents a novel form of mammalian adenylyl cyclase structurally, molecularly, and biochemically distinct from the G protein-regulated, transmembrane adenylyl cyclases (tmACs). sAC possesses no transmembrane domains and is insensitive to classic modulators of tmACs, such as heterotrimeric G proteins and P site ligands. Thus, sAC defines an independently regulated cAMP signaling system within mammalian cells. sAC is directly stimulated by bicarbonate ion both in vivo in heterologously expressing cells and in vitro using purified protein. sAC appears to be the predominant form of adenylyl cyclase (AC) in mammalian sperm, and its direct activation by bicarbonate provides a mechanism for generating the cAMP required to complete the bicarbonate-induced processes necessary for fertilization, including hyperactivated motility, capacitation, and the acrosome reaction. Immunolocalization studies reveal sAC is also abundantly expressed in other tissues which respond to bicarbonate or carbon dioxide levels suggesting it may function as a general bicarbonate/CO(2) sensor throughout the body.
Subject(s)
Adenylyl Cyclases/physiology , Bicarbonates/metabolism , Animals , Cyclic AMP/physiology , Humans , Male , Signal Transduction/physiology , Solubility , Spermatozoa/enzymology , Spermatozoa/metabolismABSTRACT
To accommodate both high sensitivity as well as the ability to respond to a broad range of stimulus concentrations, an organism must possess some means of modulating the gain of its sensory systems. This phenomenon is known as adaptation. Here, we demonstrate that Drosophila larvae can adapt to three odorants in a behavioral paradigm. Larval olfactory adaptation is concentration- and dose-dependent. Olfactory and visual adaptation in Drosophila melanogaster adults is dependent on the transient receptor potential (trp) calcium channel. Recovery from olfactory adaptation, which is TRP-dependent in adults, is shown to be unaffected by a loss-of-function trp mutation in larvae. Moreover, the TRP gene product is not expressed in the larval olfactory organs. These observations suggest a role for trp in mediating sensory function that is conserved between sensory modalities in adults but is not conserved between developmental stages.