Rose Z. Hill | University of California, Berkeley (original) (raw)

Papers by Rose Z. Hill

Research paper thumbnail of Nerve‐associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo

Research paper thumbnail of Getting in Touch with Mechanical Pain Mechanisms

Research paper thumbnail of A trio of ion channels takes the heat

Research paper thumbnail of Author response: The signaling lipid sphingosine 1-phosphate regulates mechanical pain

Research paper thumbnail of S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways

Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic... more Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous pain, but its role in itch has not yet been studied. Here we find that S1P triggers itch and pain in mice in a concentration-dependent manner, with low levels triggering acute itch alone, and high levels triggering both pain and itch. Calcium imaging and electrophysiological experiments revealed that S1P signals via S1PR3 and TRPA1 in a subset of pruriceptors, and via S1PR3 and TRPV1 in a subset of heat nociceptors. And in behavioral assays, S1P-evoked itch was selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity were selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and pain. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch an...

Research paper thumbnail of The signaling lipid sphingosine 1-phosphate regulates mechanical pain

eLife

Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to no... more Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitab...

Research paper thumbnail of Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itc... more Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the early development of itch, and the acute-to-chronic itch transition, remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch behaviors in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching behaviors in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including upregulation of inflammatory cytokines, skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of activity-induced genes and markers of neuropathic itch. Finally, we demonstrate that induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory ...

Research paper thumbnail of Optical control of sphingosine-1-phosphate formation and function

Research paper thumbnail of A teaching laboratory on the activation of xenobiotic transporters at fertilization of sea urchins

Research paper thumbnail of A TREK to Translate Genetics to Mechanisms of Migraine

Neuron

In this issue of Neuron, Royal et al. (2018) find that a mutant form of the TRESK ion channel lin... more In this issue of Neuron, Royal et al. (2018) find that a mutant form of the TRESK ion channel linked to migraine undergoes alternative translation to produce an inhibitory protein that blocks TREK channels, leading to neuronal hyperexcitability and migraine in rodents.

Research paper thumbnail of Montagna Symposium 2016-The Skin: Our Sensory Organ for Itch, Pain, Touch, and Pleasure

The Journal of investigative dermatology, Jul 1, 2017

Research paper thumbnail of S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways

The Journal of Neuroscience

Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic... more Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous pain, but its role in itch has not yet been studied. Here, we find that S1P triggers itch and pain in male mice in a concentration-dependent manner, with low levels triggering acute itch alone and high levels triggering both pain and itch. Ca 2ϩ imaging and electrophysiological experiments revealed that S1P signals via S1P receptor 3 (S1PR3) and TRPA1 in a subset of pruriceptors and via S1PR3 and TRPV1 in a subset of heat nociceptors. Consistent with these findings, S1P-evoked itch behaviors are selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity are selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and pain. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch and pain are discriminated in the periphery.

Research paper thumbnail of Unconventional endocannabinoid signaling governs sperm activation via sex hormone progesterone

Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a ... more Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, of which the key components remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by orphan enzyme ABHD2. We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as progesterone-dependent lipid hydrolase by depleting endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. 2AG inhibits sperm calcium channel CatSper, and 2AG removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.

Research paper thumbnail of ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos

ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse s... more ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells. C5a expression depends on Delta/Notch signaling from skeletogenic mesoderm and is downstream of Gcm in the aboral NSM gene regulatory network. Long-term imaging of development reveals that C5a knockdown embryos gastrulate, but ∼90% develop a prolapse of the hindgut by the late prism stage (∼8 h after C5a protein expression normally peaks). Since C5a orthologs efflux cyclic nucleotides, and cAMP-dependent protein kinase (Sp-CAPK/PKA) is expressed in pigment cells, we examined whether C5a could be involved in gastrulation through cAMP transport. Consistent with this hypothesis, membrane-permeable pCPT-cAMP rescues the prolapse phenotype in C5a knockdown embryos, and causes archenteron hyper-invagination in control embryos. In addition, the cAMP-producing enzyme soluble adenylyl cyclase (sAC) is expressed in pigment cells, and its inhibition impairs gastrulation. Together, our data support a model in which C5a transports sAC-derived cAMP from pigment cells to control late invagination of the hindgut. Little is known about the ancestral functions of ABCC5/MRP5 transporters, and this study reveals a novel role for these proteins in mesoderm-endoderm signaling during embryogenesis.

Research paper thumbnail of Nerve‐associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo

Research paper thumbnail of Getting in Touch with Mechanical Pain Mechanisms

Research paper thumbnail of A trio of ion channels takes the heat

Research paper thumbnail of Author response: The signaling lipid sphingosine 1-phosphate regulates mechanical pain

Research paper thumbnail of S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways

Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic... more Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous pain, but its role in itch has not yet been studied. Here we find that S1P triggers itch and pain in mice in a concentration-dependent manner, with low levels triggering acute itch alone, and high levels triggering both pain and itch. Calcium imaging and electrophysiological experiments revealed that S1P signals via S1PR3 and TRPA1 in a subset of pruriceptors, and via S1PR3 and TRPV1 in a subset of heat nociceptors. And in behavioral assays, S1P-evoked itch was selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity were selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and pain. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch an...

Research paper thumbnail of The signaling lipid sphingosine 1-phosphate regulates mechanical pain

eLife

Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to no... more Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitab...

Research paper thumbnail of Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itc... more Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the early development of itch, and the acute-to-chronic itch transition, remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch behaviors in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching behaviors in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including upregulation of inflammatory cytokines, skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of activity-induced genes and markers of neuropathic itch. Finally, we demonstrate that induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory ...

Research paper thumbnail of Optical control of sphingosine-1-phosphate formation and function

Research paper thumbnail of A teaching laboratory on the activation of xenobiotic transporters at fertilization of sea urchins

Research paper thumbnail of A TREK to Translate Genetics to Mechanisms of Migraine

Neuron

In this issue of Neuron, Royal et al. (2018) find that a mutant form of the TRESK ion channel lin... more In this issue of Neuron, Royal et al. (2018) find that a mutant form of the TRESK ion channel linked to migraine undergoes alternative translation to produce an inhibitory protein that blocks TREK channels, leading to neuronal hyperexcitability and migraine in rodents.

Research paper thumbnail of Montagna Symposium 2016-The Skin: Our Sensory Organ for Itch, Pain, Touch, and Pleasure

The Journal of investigative dermatology, Jul 1, 2017

Research paper thumbnail of S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways

The Journal of Neuroscience

Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic... more Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous pain, but its role in itch has not yet been studied. Here, we find that S1P triggers itch and pain in male mice in a concentration-dependent manner, with low levels triggering acute itch alone and high levels triggering both pain and itch. Ca 2ϩ imaging and electrophysiological experiments revealed that S1P signals via S1P receptor 3 (S1PR3) and TRPA1 in a subset of pruriceptors and via S1PR3 and TRPV1 in a subset of heat nociceptors. Consistent with these findings, S1P-evoked itch behaviors are selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity are selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and pain. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch and pain are discriminated in the periphery.

Research paper thumbnail of Unconventional endocannabinoid signaling governs sperm activation via sex hormone progesterone

Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a ... more Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, of which the key components remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by orphan enzyme ABHD2. We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as progesterone-dependent lipid hydrolase by depleting endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. 2AG inhibits sperm calcium channel CatSper, and 2AG removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.

Research paper thumbnail of ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos

ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse s... more ATP-binding cassette (ABC) transporters are evolutionarily conserved proteins that pump diverse substrates across membranes. Many are known to efflux signaling molecules and are extensively expressed during development. However, the role of transporters in moving extracellular signals that regulate embryogenesis is largely unexplored. Here, we show that a mesodermal ABCC (MRP) transporter is necessary for endodermal gut morphogenesis in sea urchin embryos. This transporter, Sp-ABCC5a (C5a), is expressed in pigment cells and their precursors, which are a subset of the non-skeletogenic mesoderm (NSM) cells. C5a expression depends on Delta/Notch signaling from skeletogenic mesoderm and is downstream of Gcm in the aboral NSM gene regulatory network. Long-term imaging of development reveals that C5a knockdown embryos gastrulate, but ∼90% develop a prolapse of the hindgut by the late prism stage (∼8 h after C5a protein expression normally peaks). Since C5a orthologs efflux cyclic nucleotides, and cAMP-dependent protein kinase (Sp-CAPK/PKA) is expressed in pigment cells, we examined whether C5a could be involved in gastrulation through cAMP transport. Consistent with this hypothesis, membrane-permeable pCPT-cAMP rescues the prolapse phenotype in C5a knockdown embryos, and causes archenteron hyper-invagination in control embryos. In addition, the cAMP-producing enzyme soluble adenylyl cyclase (sAC) is expressed in pigment cells, and its inhibition impairs gastrulation. Together, our data support a model in which C5a transports sAC-derived cAMP from pigment cells to control late invagination of the hindgut. Little is known about the ancestral functions of ABCC5/MRP5 transporters, and this study reveals a novel role for these proteins in mesoderm-endoderm signaling during embryogenesis.