Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope
A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular m...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713001228 |
| _version_ | 1818029299588923392 |
|---|---|
| author | Vahbiz Jokhi James Ashley John Nunnari Akiko Noma Naoto Ito Noriko Wakabayashi-Ito Melissa J. Moore Vivian Budnik |
| author_facet | Vahbiz Jokhi James Ashley John Nunnari Akiko Noma Naoto Ito Noriko Wakabayashi-Ito Melissa J. Moore Vivian Budnik |
| author_sort | Vahbiz Jokhi |
| collection | DOAJ |
| description | A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown. Here, we identify Torsin, an AAA-ATPase that in humans is linked to dystonia, as a major mediator of primary megaRNP envelopment during NE budding. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the messenger RNAs contained within fail to reach synaptic sites, preventing normal synaptic protein synthesis and thus proper synaptic bouton development. These studies begin to establish the cellular machinery underlying the exit of megaRNPs via budding, offer an explanation for the “nuclear blebbing” phenotype found in dystonia models, and provide an important link between Torsin and the synaptic phenotypes observed in dystonia. |
| first_indexed | 2024-12-10T05:17:29Z |
| format | Article |
| id | doaj.art-0935ec74da864d77939b924ff64c9c52 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T05:17:29Z |
| publishDate | 2013-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0935ec74da864d77939b924ff64c9c522022-12-22T02:00:55ZengElsevierCell Reports2211-12472013-04-013498899510.1016/j.celrep.2013.03.015Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear EnvelopeVahbiz Jokhi0James Ashley1John Nunnari2Akiko Noma3Naoto Ito4Noriko Wakabayashi-Ito5Melissa J. Moore6Vivian Budnik7Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USARNA and Neuro Therapeutics Institutes, Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Neurology and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USADepartment of Neurology and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USARNA and Neuro Therapeutics Institutes, Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USAA previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown. Here, we identify Torsin, an AAA-ATPase that in humans is linked to dystonia, as a major mediator of primary megaRNP envelopment during NE budding. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the messenger RNAs contained within fail to reach synaptic sites, preventing normal synaptic protein synthesis and thus proper synaptic bouton development. These studies begin to establish the cellular machinery underlying the exit of megaRNPs via budding, offer an explanation for the “nuclear blebbing” phenotype found in dystonia models, and provide an important link between Torsin and the synaptic phenotypes observed in dystonia.http://www.sciencedirect.com/science/article/pii/S2211124713001228 |
| spellingShingle | Vahbiz Jokhi James Ashley John Nunnari Akiko Noma Naoto Ito Noriko Wakabayashi-Ito Melissa J. Moore Vivian Budnik Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope Cell Reports |
| title | Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope |
| title_full | Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope |
| title_fullStr | Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope |
| title_full_unstemmed | Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope |
| title_short | Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope |
| title_sort | torsin mediates primary envelopment of large ribonucleoprotein granules at the nuclear envelope |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713001228 |
| work_keys_str_mv | AT vahbizjokhi torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT jamesashley torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT johnnunnari torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT akikonoma torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT naotoito torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT norikowakabayashiito torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT melissajmoore torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope AT vivianbudnik torsinmediatesprimaryenvelopmentoflargeribonucleoproteingranulesatthenuclearenvelope |