{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:49:35Z","timestamp":1782280175628,"version":"3.54.5"},"posted":{"date-parts":[[2024,12,30]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>\n                    To determine the age-of-onset and tissue-specific roles of\n                    <jats:italic>VPS13A<\/jats:italic>\n                    and\n                    <jats:italic>BLTP2<\/jats:italic>\n                    in movement disorder pathogenesis using\n                    <jats:italic>Drosophila<\/jats:italic>\n                    models.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We generated tissue-specific knockdowns of the\n                    <jats:italic>VPS13A<\/jats:italic>\n                    ortholog (\n                    <jats:italic>Vps13<\/jats:italic>\n                    ) and the\n                    <jats:italic>BLTP2<\/jats:italic>\n                    ortholog (\n                    <jats:italic>hobbit<\/jats:italic>\n                    ) in neurons and muscles of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    . We analyzed age-dependent locomotor behavior, neurodegeneration, and synapse development and function.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Neuron-specific loss of the\n                    <jats:italic>VPS13A<\/jats:italic>\n                    ortholog caused neurodegeneration followed by age- onset movement deficits and reduced lifespan, while muscle-specific loss affected only lifespan, revealing neurodegeneration and myopathy as independent comorbidities in\n                    <jats:italic>VPS13A<\/jats:italic>\n                    disease. In contrast, neuronal loss of the\n                    <jats:italic>BLTP2<\/jats:italic>\n                    ortholog resulted in severe early-onset locomotor defects without neurodegeneration, while muscle loss impaired synaptogenesis and neurotransmission at the neuromuscular junction (NMJ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    <jats:italic>VPS13A<\/jats:italic>\n                    maintains neuronal survival, while\n                    <jats:italic>BLTP2<\/jats:italic>\n                    orchestrates synaptic development.\n                    <jats:italic>VPS13A<\/jats:italic>\n                    function in muscle does not play a role in movement defects. The phenotypic specificity of BLTP function provides mechanistic insights into distinct disease trajectories for BLTP-associated movement disorders.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.12.30.630795","type":"posted-content","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T12:51:41Z","timestamp":1735735901000},"source":"Crossref","is-referenced-by-count":2,"title":["Neurodegenerative and neurodevelopmental roles for bulk lipid transporters\n                  <i>VPS13A<\/i>\n                  and\n                  <i>BLTP2<\/i>\n                  in movement disorders"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5731-6426","authenticated-orcid":false,"given":"Sarah D.","family":"Neuman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-5729","authenticated-orcid":false,"given":"Rajan S.","family":"Thakur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0106-8336","authenticated-orcid":false,"given":"Scott J.","family":"Gratz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2259-8408","authenticated-orcid":false,"given":"Kate M.","family":"O\u2019Connor-Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-1775","authenticated-orcid":false,"given":"Arash","family":"Bashirullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025010213383414000_2024.12.30.630795v1.1","unstructured":"Peikert K , Dobson-Stone C , Rampoldi L , et al. 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