Degeneration of the Olfactory Guanylyl Cyclase D Gene during Primate Evolution

Young, Janet M.; Waters, Hang; Dong, Cora; Fülle, Hans-Jürgen; Liman, Emily R.

doi:10.1371/journal.pone.0000884

Cited by 51 publications

(32 citation statements)

References 51 publications

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“…1A) (13). Secondary structure prediction of this stretch of residues in GC-C using JPRED (30) and PSI-PRED (52). B, helical wheel representation of the linker residues (Met-761-Ala-788) of GC-C showing the amphipathic nature of the helix with a predominance of hydrophobic residues on one face of the helix and a predominance of hydrophilic residues on the other.…”

Section: Resultsmentioning

confidence: 99%

The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module

Saha

Biswas

Kondapalli

et al. 2009

Journal of Biological Chemistry

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Receptor guanylyl cyclases are multidomain proteins, and ligand binding to the extracellular domain increases the levels of intracellular cGMP. The intracellular domain of these receptors is composed of a kinase homology domain (KHD), a linker of ϳ70 amino acids, followed by the C-terminal guanylyl cyclase domain. Mechanisms by which these receptors are allosterically regulated by ligand binding to the extracellular domain and ATP binding to the KHD are not completely understood. Here we examine the role of the linker region in receptor guanylyl cyclases by a series of point mutations in receptor guanylyl cyclase C. The linker region is predicted to adopt a coiled coil structure and aid in dimerization, but we find that the effects of mutations neither follow a pattern predicted for a coiled coil peptide nor abrogate dimerization. Importantly, this region is critical for repressing the guanylyl cyclase activity of the receptor in the absence of ligand and permitting ligand-mediated activation of the cyclase domain. Mutant receptors with high basal guanylyl cyclase activity show no further activation in the presence of non-ionic detergents, suggesting that hydrophobic interactions in the basal and inactive conformation of the guanylyl cyclase domain are disrupted by mutation. Equivalent mutations in the linker region of guanylyl cyclase A also elevated the basal activity and abolished ligand-and detergent-mediated activation. We, therefore, have defined a key regulatory role for the linker region of receptor guanylyl cyclases which serves as a transducer of information from the extracellular domain via the KHD to the catalytic domain.In transmembrane receptors a series of conformational changes are required to transmit the information of ligand binding (an extracellular signal) to the interior of the cell, resulting in either altered interaction with signaling intermediates or in the regulation of a catalytic activity present in the receptor. In these multidomain receptors, where the ligand binding and effector domains are present in the same polypeptide chain, the relay of conformational changes is under the exquisite control of post-translational modifications or precise structural alterations.Receptor guanylyl cyclases (GCs) 4 have an N-terminal extracellular ligand binding domain, a single transmembrane domain, and a C-terminal intracellular domain (1). Binding of ligands to the extracellular domain elicits a conformational change that increases the guanylyl cyclase activity of the receptor, resulting in increased cGMP production. The intracellular domain of receptor GCs contains a region that shares considerable sequence similarity to protein kinases and is referred to as the kinase homology domain (KHD). Binding of ATP to the KHD induces a conformational change that regulates cGMP production by the guanylyl cyclase domain (2). Thus, receptor GCs exemplify the intricate interactions between domains in transducing the signal from an extracellular ligand to the interior of the cell.The amino acid sequences of ...

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Section: Resultsmentioning

confidence: 99%

The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module

Saha

Biswas

Kondapalli

et al. 2009

Journal of Biological Chemistry

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“…Although the Ms4a genes are conserved across vertebrates, Gucy2d is itself pseudogenized in most primates (Young et al, 2007). It is unclear if the absence of GC-D reflects a disappearance of the necklace system in primates or merely that GC-D became unnecessary for the tasks required of the primate necklace, given the persistence of the Ms4a genes (Young et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

A Family of non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction

Greer

Bear

Lassance

et al. 2016

Cell

133

134

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Summary Odor perception in mammals is mediated by parallel sensory pathways that convey distinct information about the olfactory world. Multiple olfactory subsystems express characteristic seven-transmembrane G-protein coupled receptors (GPCRs) in a one-receptor-per-neuron pattern that facilitates odor discrimination. Sensory neurons of the “necklace” subsystem are nestled within the recesses of the olfactory epithelium and detect diverse odorants; however, they do not express known GPCR odor receptors. Here we report that members of the four-pass transmembrane MS4A protein family are chemosensors expressed within necklace sensory neurons. These receptors localize to sensory endings and confer responses to ethologically-relevant ligands including pheromones and fatty acids in vitro and in vivo. Individual necklace neurons co-express many MS4A proteins and are activated by multiple MS4A ligands; this pooling of information suggests that the necklace is organized more like subsystems for taste than for smell. The MS4As therefore define a distinct mechanism and functional logic for mammalian olfaction.

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“…The rat sequences were obtained from the 2004 Rattus genome release. Sequences for six primate taxa were obtained from their genomes using the method of Young et al (2007). …”

Section: Dna Amplification and Sequencing Of Svs Genesmentioning

confidence: 99%

Adaptive Evolution in Rodent Seminal Vesicle Secretion Proteins

Karn¹,

Clark²,

Nguyen³

et al. 2008

Molecular Biology and Evolution

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Proteins involved in reproductive fitness have evolved unusually rapidly across diverse groups of organisms. These reproductive proteins show unusually high rates of amino acid substitutions, suggesting that the proteins have been subject to positive selection. We sought to identify seminal fluid proteins experiencing adaptive evolution because such proteins are often involved in sperm competition, host immunity to pathogens, and manipulation of female reproductive physiology and behavior. We performed an evolutionary screen of the mouse prostate transcriptome for genes with elevated evolutionary rates between mouse and rat. We observed that secreted rodent prostate proteins evolve approximately twice as fast as nonsecreted proteins, remarkably similar to findings in the primate prostate and in the Drosophila male accessory gland. Our screen led us to identify and characterize a group of seminal vesicle secretion (Svs) proteins and to show that the gene Svs7 is evolving very rapidly, with many amino acid sites under positive selection. Another gene in this group, Svs5, showed evidence of branch-specific selection in the rat. We also found that Svs7 is under selection in primates and, by using three-dimensional models, demonstrated that the same regions have been under selection in both groups. Svs7 has been identified as mouse caltrin, a protein involved in sperm capacitation, the process responsible for the timing of changes in sperm activity and behavior, following ejaculation. We propose that the most likely explanation of the adaptive evolution of Svs7 that we have observed in rodents and primates stems from an important function in sperm competition.

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Degeneration of the Olfactory Guanylyl Cyclase D Gene during Primate Evolution

Cited by 51 publications

References 51 publications

The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module

The Linker Region in Receptor Guanylyl Cyclases Is a Key Regulatory Module

A Family of non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction

Adaptive Evolution in Rodent Seminal Vesicle Secretion Proteins

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