Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation
Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca²+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-de...
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| Veröffentlicht in: | Science signaling 2012-04, Vol.5 (218), p.ra27-ra27 |
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| creator | Arizono, Misa Bannai, Hiroko Nakamura, Kyoko Niwa, Fumihiro Enomoto, Masahiro Matsu-Ura, Toru Miyamoto, Akitoshi Sherwood, Mark W Nakamura, Takeshi Mikoshiba, Katsuhiko |
| description | Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca²+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca²+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca²+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca²+ responses. Immunocytochemistry indicated that these polarized Ca²+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca²+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca²+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains. |
| doi_str_mv | 10.1126/scisignal.2002498 |
| format | Article |
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However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca²+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca²+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca²+ responses. Immunocytochemistry indicated that these polarized Ca²+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca²+ signaling. 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Bannai, Hiroko ; Nakamura, Kyoko ; Niwa, Fumihiro ; Enomoto, Masahiro ; Matsu-Ura, Toru ; Miyamoto, Akitoshi ; Sherwood, Mark W ; Nakamura, Takeshi ; Mikoshiba, Katsuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-8477099c22c38839eb0e4cdaa3bfdb201a04920af4249b46629d5b58412001023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Algorithms</topic><topic>Animals</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - metabolism</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling - drug effects</topic><topic>Calmodulin - genetics</topic><topic>Calmodulin - metabolism</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Diffusion</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Fluorescence Recovery After Photobleaching</topic><topic>Glycine - analogs & derivatives</topic><topic>Glycine - pharmacology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - metabolism</topic><topic>Immunohistochemistry</topic><topic>Kinetics</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Quantum Dots</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Metabotropic Glutamate 5</topic><topic>Receptors, Metabotropic Glutamate - agonists</topic><topic>Receptors, Metabotropic Glutamate - genetics</topic><topic>Receptors, Metabotropic Glutamate - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Resorcinols - pharmacology</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arizono, Misa</creatorcontrib><creatorcontrib>Bannai, Hiroko</creatorcontrib><creatorcontrib>Nakamura, Kyoko</creatorcontrib><creatorcontrib>Niwa, Fumihiro</creatorcontrib><creatorcontrib>Enomoto, Masahiro</creatorcontrib><creatorcontrib>Matsu-Ura, Toru</creatorcontrib><creatorcontrib>Miyamoto, Akitoshi</creatorcontrib><creatorcontrib>Sherwood, Mark W</creatorcontrib><creatorcontrib>Nakamura, Takeshi</creatorcontrib><creatorcontrib>Mikoshiba, Katsuhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arizono, Misa</au><au>Bannai, Hiroko</au><au>Nakamura, Kyoko</au><au>Niwa, Fumihiro</au><au>Enomoto, Masahiro</au><au>Matsu-Ura, Toru</au><au>Miyamoto, Akitoshi</au><au>Sherwood, Mark W</au><au>Nakamura, Takeshi</au><au>Mikoshiba, Katsuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation</atitle><jtitle>Science signaling</jtitle><addtitle>Sci Signal</addtitle><date>2012-04-03</date><risdate>2012</risdate><volume>5</volume><issue>218</issue><spage>ra27</spage><epage>ra27</epage><pages>ra27-ra27</pages><issn>1945-0877</issn><eissn>1937-9145</eissn><abstract>Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca²+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca²+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca²+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca²+ responses. Immunocytochemistry indicated that these polarized Ca²+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca²+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca²+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains.</abstract><cop>United States</cop><pmid>22472649</pmid><doi>10.1126/scisignal.2002498</doi></addata></record> |
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| ispartof | Science signaling, 2012-04, Vol.5 (218), p.ra27-ra27 |
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| source | MEDLINE; American Association for the Advancement of Science |
| subjects | Algorithms Animals Astrocytes - cytology Astrocytes - metabolism Calcium - metabolism Calcium Signaling - drug effects Calmodulin - genetics Calmodulin - metabolism Cells, Cultured Coculture Techniques Diffusion Excitatory Amino Acid Agonists - pharmacology Fluorescence Recovery After Photobleaching Glycine - analogs & derivatives Glycine - pharmacology Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Hippocampus - cytology Hippocampus - metabolism Immunohistochemistry Kinetics Neurons - cytology Neurons - metabolism Quantum Dots Rats Rats, Wistar Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - agonists Receptors, Metabotropic Glutamate - genetics Receptors, Metabotropic Glutamate - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Resorcinols - pharmacology Transfection |
| title | Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation |
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