The dual role of chloride in synaptic vesicle glutamate transport
The transport of glutamate into synaptic vesicles exhibits an unusual form of regulation by Cl- as well as an associated Cl- conductance. To distinguish direct effects of Cl- on the transporter from indirect effects via the driving force Δψ, we used whole endosome recording and report the first curr...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-07-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/34896 |
| _version_ | 1811253140470628352 |
|---|---|
| author | Roger Chang Jacob Eriksen Robert H Edwards |
| author_facet | Roger Chang Jacob Eriksen Robert H Edwards |
| author_sort | Roger Chang |
| collection | DOAJ |
| description | The transport of glutamate into synaptic vesicles exhibits an unusual form of regulation by Cl- as well as an associated Cl- conductance. To distinguish direct effects of Cl- on the transporter from indirect effects via the driving force Δψ, we used whole endosome recording and report the first currents due to glutamate flux by the vesicular glutamate transporters (VGLUTs). Chloride allosterically activates the VGLUTs from both sides of the membrane, and we find that neutralization of an arginine in transmembrane domain four suffices for the lumenal activation. The dose dependence suggests that Cl- permeates through a channel and glutamate through a transporter. Competition between the anions nonetheless indicates that they use a similar permeation pathway. By controlling both ionic gradients and Δψ, endosome recording isolates different steps in the process of synaptic vesicle filling, suggesting distinct roles for Cl- in both allosteric activation and permeation. |
| first_indexed | 2024-04-12T16:45:15Z |
| format | Article |
| id | doaj.art-7312981ca9d844abb37fb701eea18102 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:45:15Z |
| publishDate | 2018-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7312981ca9d844abb37fb701eea181022022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.34896The dual role of chloride in synaptic vesicle glutamate transportRoger Chang0https://orcid.org/0000-0001-5654-2480Jacob Eriksen1https://orcid.org/0000-0003-0726-9769Robert H Edwards2https://orcid.org/0000-0002-8650-3260Department of Physiology, UCSF School of Medicine, San Francisco, United States; Department of Neurology, UCSF School of Medicine, San Francisco, United States; Graduate Program in Biomedical Sciences, UCSF School of Medicine, San Francisco, United StatesDepartment of Physiology, UCSF School of Medicine, San Francisco, United States; Department of Neurology, UCSF School of Medicine, San Francisco, United StatesDepartment of Physiology, UCSF School of Medicine, San Francisco, United States; Department of Neurology, UCSF School of Medicine, San Francisco, United States; Graduate Program in Biomedical Sciences, UCSF School of Medicine, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, UCSF School of Medicine, San Francisco, United States; Weill Institute for Neurosciences, UCSF School of Medicine, San Francisco, United StatesThe transport of glutamate into synaptic vesicles exhibits an unusual form of regulation by Cl- as well as an associated Cl- conductance. To distinguish direct effects of Cl- on the transporter from indirect effects via the driving force Δψ, we used whole endosome recording and report the first currents due to glutamate flux by the vesicular glutamate transporters (VGLUTs). Chloride allosterically activates the VGLUTs from both sides of the membrane, and we find that neutralization of an arginine in transmembrane domain four suffices for the lumenal activation. The dose dependence suggests that Cl- permeates through a channel and glutamate through a transporter. Competition between the anions nonetheless indicates that they use a similar permeation pathway. By controlling both ionic gradients and Δψ, endosome recording isolates different steps in the process of synaptic vesicle filling, suggesting distinct roles for Cl- in both allosteric activation and permeation.https://elifesciences.org/articles/34896vesicular glutamate transportneurotransmitter packagingendosome recordingallosteric activationchloridechloride conductance |
| spellingShingle | Roger Chang Jacob Eriksen Robert H Edwards The dual role of chloride in synaptic vesicle glutamate transport eLife vesicular glutamate transport neurotransmitter packaging endosome recording allosteric activation chloride chloride conductance |
| title | The dual role of chloride in synaptic vesicle glutamate transport |
| title_full | The dual role of chloride in synaptic vesicle glutamate transport |
| title_fullStr | The dual role of chloride in synaptic vesicle glutamate transport |
| title_full_unstemmed | The dual role of chloride in synaptic vesicle glutamate transport |
| title_short | The dual role of chloride in synaptic vesicle glutamate transport |
| title_sort | dual role of chloride in synaptic vesicle glutamate transport |
| topic | vesicular glutamate transport neurotransmitter packaging endosome recording allosteric activation chloride chloride conductance |
| url | https://elifesciences.org/articles/34896 |
| work_keys_str_mv | AT rogerchang thedualroleofchlorideinsynapticvesicleglutamatetransport AT jacoberiksen thedualroleofchlorideinsynapticvesicleglutamatetransport AT roberthedwards thedualroleofchlorideinsynapticvesicleglutamatetransport AT rogerchang dualroleofchlorideinsynapticvesicleglutamatetransport AT jacoberiksen dualroleofchlorideinsynapticvesicleglutamatetransport AT roberthedwards dualroleofchlorideinsynapticvesicleglutamatetransport |