PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids
The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520600335 |
| _version_ | 1818661889680343040 |
|---|---|
| author | Hideaki Kuge Izumi Miyamoto Ken-ichi Yagyu Koichi Honke |
| author_facet | Hideaki Kuge Izumi Miyamoto Ken-ichi Yagyu Koichi Honke |
| author_sort | Hideaki Kuge |
| collection | DOAJ |
| description | The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain. |
| first_indexed | 2024-12-17T04:52:14Z |
| format | Article |
| id | doaj.art-c77d7188514d4485b10f1526807114cd |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T04:52:14Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c77d7188514d4485b10f1526807114cd2022-12-21T22:02:52ZengElsevierJournal of Lipid Research0022-22752020-12-01611217471763PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipidsHideaki Kuge0Izumi Miyamoto1Ken-ichi Yagyu2Koichi Honke3Department of Biochemistry, Kochi University Medical School, Nankoku, Kochi, Japan; For correspondence: Hideaki Kuge; Koichi Honke; For correspondence: Hideaki Kuge; Koichi HonkeDepartment of Biochemistry, Kochi University Medical School, Nankoku, Kochi, JapanScience Research Center, Kochi University Medical School, Nankoku, Kochi, JapanDepartment of Biochemistry, Kochi University Medical School, Nankoku, Kochi, Japan; For correspondence: Hideaki Kuge; Koichi Honke; For correspondence: Hideaki Kuge; Koichi HonkeThe plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.http://www.sciencedirect.com/science/article/pii/S0022227520600335glycerophospholipidsmembrane lipidsmembranes/fluidityphospholipasesphospholipid remodelingacyl-chain configuration |
| spellingShingle | Hideaki Kuge Izumi Miyamoto Ken-ichi Yagyu Koichi Honke PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids Journal of Lipid Research glycerophospholipids membrane lipids membranes/fluidity phospholipases phospholipid remodeling acyl-chain configuration |
| title | PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids |
| title_full | PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids |
| title_fullStr | PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids |
| title_full_unstemmed | PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids |
| title_short | PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids |
| title_sort | plrp2 selectively localizes synaptic membrane proteins via acyl chain remodeling of phospholipids |
| topic | glycerophospholipids membrane lipids membranes/fluidity phospholipases phospholipid remodeling acyl-chain configuration |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520600335 |
| work_keys_str_mv | AT hideakikuge plrp2selectivelylocalizessynapticmembraneproteinsviaacylchainremodelingofphospholipids AT izumimiyamoto plrp2selectivelylocalizessynapticmembraneproteinsviaacylchainremodelingofphospholipids AT kenichiyagyu plrp2selectivelylocalizessynapticmembraneproteinsviaacylchainremodelingofphospholipids AT koichihonke plrp2selectivelylocalizessynapticmembraneproteinsviaacylchainremodelingofphospholipids |