Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions
In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-07-01
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| Series: | Contact |
| Online Access: | https://doi.org/10.1177/25152564231186489 |
| _version_ | 1797782359527915520 |
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| author | Taruna Pandey Jianxiu Zhang Bingying Wang Dengke K. Ma |
| author_facet | Taruna Pandey Jianxiu Zhang Bingying Wang Dengke K. Ma |
| author_sort | Taruna Pandey |
| collection | DOAJ |
| description | In eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for diverse cellular processes, including lipid metabolism, membrane trafficking, and cell signaling. BLTPs (BLTP1-5, including the ATG2 and VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow the bulk transfer of lipids through MCS. Compared with vesicular lipid transfer and shuttle LTP, BLTPs have been only recently identified. Their functions and regulatory mechanisms are currently being unraveled in various model organisms and by diverse approaches. In this review, we summarize the genetics, structural features, and biological functions of BLTP in the genetically tractable model organism C. elegans . We discuss our recent studies and findings on C. elegans LPD-3, a prototypical megaprotein ortholog of BLTP1, with identified lipid transfer functions that are evolutionarily conserved in multicellular organisms and in human cells. We also highlight areas for future research of BLTP using C. elegans and complementary model systems and approaches. Given the emerging links of BLTP to several human diseases, including Parkinson's disease and Alkuraya-Kučinskas syndrome, discovering evolutionarily conserved roles of BLTPs and their mechanisms of regulation and action should contribute to new advances in basic cell biology and potential therapeutic development for related human disorders. |
| first_indexed | 2024-03-13T00:09:52Z |
| format | Article |
| id | doaj.art-a5878d8e45034411951c435916b0f111 |
| institution | Directory Open Access Journal |
| issn | 2515-2564 |
| language | English |
| last_indexed | 2024-03-13T00:09:52Z |
| publishDate | 2023-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Contact |
| spelling | doaj.art-a5878d8e45034411951c435916b0f1112023-07-12T18:33:29ZengSAGE PublishingContact2515-25642023-07-01610.1177/25152564231186489Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and FunctionsTaruna Pandey0Jianxiu Zhang1Bingying Wang2 Dengke K. Ma3 Cardiovascular Research Institute and Department of Physiology, , San Francisco, USA Department of Molecular and Cellular Physiology, , Stanford, CA, USA Cardiovascular Research Institute and Department of Physiology, , San Francisco, USA Cardiovascular Research Institute and Department of Physiology, , San Francisco, USAIn eukaryotic cells, lipid transfer can occur at membrane contact sites (MCS) to facilitate the exchange of various lipids between two adjacent cellular organelle membranes. Lipid transfer proteins (LTPs), including shuttle LTP or bridge-like LTP (BLTP), transport lipids at MCS and are critical for diverse cellular processes, including lipid metabolism, membrane trafficking, and cell signaling. BLTPs (BLTP1-5, including the ATG2 and VPS13 family proteins) contain lipid-accommodating hydrophobic repeating β-groove (RBG) domains that allow the bulk transfer of lipids through MCS. Compared with vesicular lipid transfer and shuttle LTP, BLTPs have been only recently identified. Their functions and regulatory mechanisms are currently being unraveled in various model organisms and by diverse approaches. In this review, we summarize the genetics, structural features, and biological functions of BLTP in the genetically tractable model organism C. elegans . We discuss our recent studies and findings on C. elegans LPD-3, a prototypical megaprotein ortholog of BLTP1, with identified lipid transfer functions that are evolutionarily conserved in multicellular organisms and in human cells. We also highlight areas for future research of BLTP using C. elegans and complementary model systems and approaches. Given the emerging links of BLTP to several human diseases, including Parkinson's disease and Alkuraya-Kučinskas syndrome, discovering evolutionarily conserved roles of BLTPs and their mechanisms of regulation and action should contribute to new advances in basic cell biology and potential therapeutic development for related human disorders.https://doi.org/10.1177/25152564231186489 |
| spellingShingle | Taruna Pandey Jianxiu Zhang Bingying Wang Dengke K. Ma Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions Contact |
| title | Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions |
| title_full | Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions |
| title_fullStr | Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions |
| title_full_unstemmed | Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions |
| title_short | Bridge-Like Lipid Transfer Proteins (BLTPs) in : From Genetics to Structures and Functions |
| title_sort | bridge like lipid transfer proteins bltps in from genetics to structures and functions |
| url | https://doi.org/10.1177/25152564231186489 |
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