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Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension

ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in...

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Autores principales: Pantakani, D. V. Krishna, Czyzewska, Marta M., Sikorska, Anna, Bodda, Chiranjeevi, Mannan, Ashraf U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247280/
https://www.ncbi.nlm.nih.gov/pubmed/22216323
http://dx.doi.org/10.1371/journal.pone.0029584
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author Pantakani, D. V. Krishna
Czyzewska, Marta M.
Sikorska, Anna
Bodda, Chiranjeevi
Mannan, Ashraf U.
author_facet Pantakani, D. V. Krishna
Czyzewska, Marta M.
Sikorska, Anna
Bodda, Chiranjeevi
Mannan, Ashraf U.
author_sort Pantakani, D. V. Krishna
collection PubMed
description ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(ΔHR3) failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(ΔHR3) was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT)), it exerted a dominant negative effect on ZFYVE27(WT) as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions.
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spelling pubmed-32472802012-01-03 Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension Pantakani, D. V. Krishna Czyzewska, Marta M. Sikorska, Anna Bodda, Chiranjeevi Mannan, Ashraf U. PLoS One Research Article ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(ΔHR3) failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(ΔHR3) was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT)), it exerted a dominant negative effect on ZFYVE27(WT) as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions. Public Library of Science 2011-12-28 /pmc/articles/PMC3247280/ /pubmed/22216323 http://dx.doi.org/10.1371/journal.pone.0029584 Text en Pantakani et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pantakani, D. V. Krishna
Czyzewska, Marta M.
Sikorska, Anna
Bodda, Chiranjeevi
Mannan, Ashraf U.
Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title_full Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title_fullStr Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title_full_unstemmed Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title_short Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
title_sort oligomerization of zfyve27 (protrudin) is necessary to promote neurite extension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247280/
https://www.ncbi.nlm.nih.gov/pubmed/22216323
http://dx.doi.org/10.1371/journal.pone.0029584
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