A Specific Heat Shock Protein Enhances the Expression of Mammalian Olfactory Receptor Proteins

Neuhaus, Eva M.; Mashukova, Anastasia; Zhang, Weiyi; Barbour, Jon; Hatt, Hanns

doi:10.1093/chemse/bjj049

Cited by 88 publications

(70 citation statements)

References 56 publications

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“…OR2AG1-RLuc plasmid was obtained by subcloning the coding sequences of Renilla luciferase (RLuc) from the plasmid pGFP2-multiple cloning site-RLuc(h) (Packard BioScience, Meriden, CT) into the ClaIlinearized, odorant-receptor-containing plasmid. The OR2AG1-GFP and OR2AG1-RLuc fusion proteins were tested for functionality by Ca 2ϩ imaging using amylbutyrat (Neuhaus et al, 2006).…”

Section: Methodsmentioning

confidence: 99%

“…To investigate whether ORs also undergo regulated internalization from the cell surface, trafficking of recombinant OR2AG1-GFP fusion protein was analyzed in heterologous cells by confocal microscopy. Treatment with its cognate ligand amylbutyrat (Neuhaus et al, 2006) resulted in redistribution of OR2AG1-GFP from the plasma membrane to intracellular vesicles ( Fig. 1 A, B).…”

Section: Activated Ors Are Internalized and Accumulate In Recycling Ementioning

confidence: 98%

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β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Mashukova¹,

Spehr²,

Hatt³

et al. 2006

J. Neurosci.

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␤-arrestin2 with high affinity and are internalized via a clathrin-dependent mechanism. After prolonged odorant exposure, receptors are not targeted to lysosomal degradation but accumulate in recycling endosomes. Odorant-induced odorant receptor desensitization is promoted by cAMPdependent protein kinase A phosphorylation and is dependent on serine and threonine residues within the third intracellular loop of the receptor. Moreover, ␤-arrestin2 is redistributed into the dendritic knobs of mouse olfactory receptor neurons after treatment with a complex odorant mixture. Prolonged odorant exposure resulted in accumulation of ␤-arrestin2 in intracellular vesicles. Adaptation of olfactory receptor neurons to odorants can be abolished by the inhibition of clathrin-mediated endocytosis, showing the physiological relevance of the here described mechanism of odorant receptor desensitization. A better understanding of odorant receptor trafficking and additional insight into the molecular determinants underlying the interactions of odorant receptors with ␤-arrestin2 and other trafficking proteins will therefore be important to fully understand the mechanisms of adaptation and sensitization in the olfactory epithelium.

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Section: Methodsmentioning

confidence: 99%

Section: Activated Ors Are Internalized and Accumulate In Recycling Ementioning

confidence: 98%

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Mashukova¹,

Spehr²,

Hatt³

et al. 2006

J. Neurosci.

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“…Those cells that functionally expressed either OR7A5 or OR4D1 displayed robust Ca 2ϩ signals when exposed to the stimulus mixture (data not shown), whereas stimulus-dependent Ca 2ϩ responses were never observed in nontransfected cells. We then divided the stimulus into different submixtures (17,(55)(56)(57) and determined the specific fraction activating either OR7A5 or OR4D1, respectively. After several such cycles, we identified two receptor-ligand pairs.…”

Section: Distinct Agonist Profiles Of Three Human Testicularmentioning

confidence: 99%

Chemosensory Ca2+ Dynamics Correlate with Diverse Behavioral Phenotypes in Human Sperm

Veitinger

Riffell

Veitinger

et al. 2011

Journal of Biological Chemistry

115

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In the female reproductive tract, mammalian sperm undergo a regulated sequence of prefusion changes that "prime" sperm for fertilization. Among the least understood of these complex processes are the molecular mechanisms that underlie sperm guidance by environmental chemical cues. A "hard-wired" Ca 2؉ signaling strategy that orchestrates specific motility patterns according to given functional requirements is an emerging concept for regulation of sperm swimming behavior. The molecular players involved, the spatiotemporal characteristics of such motility-associated Ca 2؉ dynamics, and the relation between a distinct Ca 2؉ signaling pattern and a behavioral sperm phenotype, however, remain largely unclear. Here, we report the functional characterization of two human sperm chemoreceptors. Using complementary molecular, physiological, and behavioral approaches, we comparatively describe sperm Ca 2؉ responses to specific agonists of these novel receptors and bourgeonal, a known sperm chemoattractant. We further show that individual receptor activation induces specific Ca 2؉ signaling patterns with unique spatiotemporal dynamics. These distinct Ca 2؉ dynamics are correlated to a set of stimulus-specific stereotyped behavioral responses that could play vital roles during various stages of prefusion sperm-egg chemical communication.On their journey to locate the oocyte, navigating mammalian sperm depend on both chemical (1) and physical (2, 3) cues to regulate flagellar motion, switch flagellar beat modes, and, thus, direct their movement. How such environmental signals are detected and translated into changes in motility, however, remains largely unknown.Sperm acquire motility upon vaginal deposition (4). This initial swimming behavior is referred to as activated motility and characterized by a relatively low amplitude/high frequency sinusoidal flagellar motion (5). Motile sperm that pass the cervical mucus barrier must locate and enter the oviduct. Only a fraction of sperm present in the uterus (ϳ10% in humans (6)) accomplishes this task. Within the oviductal isthmus, sperm frequently attach to the highly convoluted epithelial surface (3,7,8), forming a sperm reservoir in close proximity to the fertilization site. Upon ovulation, capacitated sperm that adopt a hyperactivated state (i.e. displaying asymmetrical and relatively high amplitude/low frequency flagellar beating) (4), generate sufficient propulsion force to detach from the epithelium, enter the ampulla, and eventually penetrate the cumulus and zona pellucida surrounding the egg (9).Given the small fraction of sperm that reaches the oviduct, a "competitive race" scenario has fallen out of favor in recent years. Instead, effective sperm guidance mechanisms are required to assure a synchronized arrival and encounter of both gametes at the fertilization site (1). Current models propose a complex multistep process of sperm navigation along thermal (2) and chemical (10) gradients. Accordingly, chemical guidance cues are secreted by both the oocyte and the surroundi...

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“…Hsp70 proteins have been suggested to promote the processing of both wild-type and mutant GPCRs to the PM. For example, the testis enriched Hsp70 variant, Hsc70t/HspA1L, enhances the expression and trafficking to the cell surface of odorant receptors (Neuhaus et al 2006); whilst Hsc70 has been demonstrated to interact with cytoplasmic domains of non-glycosylated angiotensin II type 1 receptor (Lanctot et al 2006). Furthermore, in cultured cells, the Hsp70 cochaperone HSJ1b can modulate the processing of the archetypal GPCR rhodopsin.…”

Section: Molecular Chaperones As Regulators Of Protein Degradationmentioning

confidence: 99%

From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery

Meimaridou

Gooljar²,

Chapple³

2008

Journal of Molecular Endocrinology

116

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Molecular chaperones are best recognized for their roles in de novo protein folding and the cellular response to stress. However, many molecular chaperones, and in particular the Hsp70 chaperone machinery, have multiple diverse cellular functions. At the molecular level, chaperones are mediators of protein conformational change. To facilitate conformational change of client/substrate proteins, in manifold contexts, chaperone power must be closely regulated and harnessed to specific cellular locales -this is controlled by cochaperones. This review considers specialized functions of the Hsp70 chaperone machinery mediated by its cochaperones. We focus on vesicular trafficking, protein degradation and a potential role in G protein-coupled receptor processing.

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A Specific Heat Shock Protein Enhances the Expression of Mammalian Olfactory Receptor Proteins

Cited by 88 publications

References 56 publications

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Chemosensory Ca2+ Dynamics Correlate with Diverse Behavioral Phenotypes in Human Sperm

From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery

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