{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86808"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86808","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"α-Synuclein and Leucine Rich Repeat Kinase 2 (LRRK2) Interaction During Axonal Transport","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Chakraborty, Piyali; 0000-0003-0862-3280"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gunawardena, Shermali","Neuroscience"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-25T23:22:58Z","date_published":"2025-02-25T23:22:58Z","updated_at":"2026-07-27T19:05:37Z","subjects":["biology","neurosciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86808","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gunawardena, Shermali","Neuroscience"]},{"key":"dc:creator","label":"Author","values":["Chakraborty, Piyali; 0000-0003-0862-3280"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-25T23:22:58Z","2020","2020-07-14 12:53:33"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["biology","neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86808"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Axonal transport involves transfer of essential material to and from the cell body and synapse of a neuron via molecular motors Kinesin and Dynein. Any alteration in this pathway results in axonal transport defects which have been implicated as an early event in neurodegenerative diseases including Parkinson's disease (PD). One of the pathological hallmarks of PD is the presence of alpha-synuclein (α-syn) containing Lewy bodies. Another protein known as a causative factor for PD is LRRK2. LRRK2 (leucine rich repeat kinase-2), a serine/threonine kinase with dual enzymatic activity of kinase and GTPase that has been suggested to phosphorylate α-syn at Serine 129 position. LRRK2 also has been shown to localize in the periphery of Lewy Bodies. However, little is known if α-syn and LRRK2 interact and whether this interaction influences α-syn and synaptic vesicle transport. Using Drosophila as a model system, we observed that excess human α-syn-EGFP caused transport defects as indicated by the EGFP positive axonal accumulations along the segmental nerves. To identify how LRRK2 affects the transport of α-syn, we co-expressed α-syn-EGFP with LRRK2-WT, kinase domain mutants (LRRK2-G2019S and LRRK2-I2020T), GTPase domain mutant (LRRK2-Y1699C) and WD40 domain mutant (LRRK2-G2385R) in third instar Drosophila larval neurons. Co-expression of human α-syn-EGFP-WT with hLRRK2-WT decreased α-syn-positive axonal blockages. A similar rescue phenotype was also observed in larvae co-expressing α-syn-WT/EGFP with LRRK2 GTPase (LRRK2-Y1699C) and LRRK2 WD40 (LRRK2-G2385R) domain. However, LRRK2 kinase domain mutants (LRRK2-G2019S and LRRK2-I2020T) failed to rescue α-syn blockages. Further, human α-syn-WT was co-expressed with human LRRK2-WT and its domain specific mutants to find out its effects on axonal transport of SV. We observed a rescuing effect with GTPase and WD40 domain suggesting that these two domains are required for axonal transport of synaptic vesicles. It also suggests that α-syn-WT might interact to LRRK2 via these two domains. We observed an enhancing effect with kinase domain mutant LRRK2-G2019S in increasing SV mediated axonal transport defects. Together, our observations propose that α-syn and LRRK2 functionally associates via the GTPase and WD40 domain during axonal transport. We further observed that LRRK2 GTPase and WD40 as well as the kinase domains (G2019S) are required for LRRK2 mediated synaptic vesicle transport, since disruption of kinase domains significantly increases CSP (Cysteine string protein) positive axonal accumulations whereas, GTPase and WD40 domain decreases the SV accumulations. Future studies will be based on knowing the functional interaction between LRRK2 GTPase and WD40 domain with α-synuclein biochemically.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["α-Synuclein and Leucine Rich Repeat Kinase 2 (LRRK2) Interaction During Axonal Transport"]}]}],"canonical_facts":{"dc:contributor":["Gunawardena, Shermali","Neuroscience"],"dc:creator":["Chakraborty, Piyali; 0000-0003-0862-3280"],"dc:date":["2025-02-25T23:22:58Z","2020","2020-07-14 12:53:33"],"dc:description":["M.S.","Axonal transport involves transfer of essential material to and from the cell body and synapse of a neuron via molecular motors Kinesin and Dynein. Any alteration in this pathway results in axonal transport defects which have been implicated as an early event in neurodegenerative diseases including Parkinson's disease (PD). One of the pathological hallmarks of PD is the presence of alpha-synuclein (α-syn) containing Lewy bodies. Another protein known as a causative factor for PD is LRRK2. LRRK2 (leucine rich repeat kinase-2), a serine/threonine kinase with dual enzymatic activity of kinase and GTPase that has been suggested to phosphorylate α-syn at Serine 129 position. LRRK2 also has been shown to localize in the periphery of Lewy Bodies. However, little is known if α-syn and LRRK2 interact and whether this interaction influences α-syn and synaptic vesicle transport. Using Drosophila as a model system, we observed that excess human α-syn-EGFP caused transport defects as indicated by the EGFP positive axonal accumulations along the segmental nerves. To identify how LRRK2 affects the transport of α-syn, we co-expressed α-syn-EGFP with LRRK2-WT, kinase domain mutants (LRRK2-G2019S and LRRK2-I2020T), GTPase domain mutant (LRRK2-Y1699C) and WD40 domain mutant (LRRK2-G2385R) in third instar Drosophila larval neurons. Co-expression of human α-syn-EGFP-WT with hLRRK2-WT decreased α-syn-positive axonal blockages. A similar rescue phenotype was also observed in larvae co-expressing α-syn-WT/EGFP with LRRK2 GTPase (LRRK2-Y1699C) and LRRK2 WD40 (LRRK2-G2385R) domain. However, LRRK2 kinase domain mutants (LRRK2-G2019S and LRRK2-I2020T) failed to rescue α-syn blockages. Further, human α-syn-WT was co-expressed with human LRRK2-WT and its domain specific mutants to find out its effects on axonal transport of SV. We observed a rescuing effect with GTPase and WD40 domain suggesting that these two domains are required for axonal transport of synaptic vesicles. It also suggests that α-syn-WT might interact to LRRK2 via these two domains. We observed an enhancing effect with kinase domain mutant LRRK2-G2019S in increasing SV mediated axonal transport defects. Together, our observations propose that α-syn and LRRK2 functionally associates via the GTPase and WD40 domain during axonal transport. We further observed that LRRK2 GTPase and WD40 as well as the kinase domains (G2019S) are required for LRRK2 mediated synaptic vesicle transport, since disruption of kinase domains significantly increases CSP (Cysteine string protein) positive axonal accumulations whereas, GTPase and WD40 domain decreases the SV accumulations. Future studies will be based on knowing the functional interaction between LRRK2 GTPase and WD40 domain with α-synuclein biochemically.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86808"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["biology","neurosciences"],"dc:title":["α-Synuclein and Leucine Rich Repeat Kinase 2 (LRRK2) Interaction During Axonal Transport"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:37Z"}