6iwa

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Crystal structure of Importin-alpha and phosphoserine GM130

Structural highlights

6iwa is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:SEP
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GOGA2_HUMAN Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane. Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401).[UniProtKB:Q62839][UniProtKB:Q921M4][1] [2] [3] [4] [5] [6]

Publication Abstract from PubMed

To facilitate proper mitotic cell partitioning, the Golgi disassembles by suppressing vesicle fusion. However, the underlying mechanism has not been characterized previously. Here, we report a Ran pathway-independent attenuation mechanism that allows Importin-alpha (a nuclear transport factor) to suppress the vesicle fusion mediated by p115 (a vesicular tethering factor) and is required for mitotic Golgi disassembly. We demonstrate that Importin-alpha directly competes with p115 for interaction with the Golgi protein GM130. This interaction, promoted by a phosphate moiety on GM130, is independent of Importin-beta and Ran. A GM130 K34A mutant, in which the Importin-alpha-GM130 interaction is specifically disrupted, exhibited abundant Golgi puncta during metaphase. Importantly, a mutant showing enhanced p115-GM130 interaction presented proliferative defects and G2/M arrest, demonstrating that Importin-alpha-GM130 binding modulates the Golgi disassembly that governs mitotic progression. Our findings illuminate that the Ran and kinase-phosphatase pathways regulate multiple aspects of mitosis coordinated by Importin-alpha (e.g. spindle assembly, Golgi disassembly).

Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-alpha.,Chang CC, Chen CJ, Grauffel C, Pien YC, Lim C, Tsai SY, Hsia KC Nat Commun. 2019 Sep 20;10(1):4307. doi: 10.1038/s41467-019-12207-4. PMID:31541088[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Puthenveedu MA, Bachert C, Puri S, Lanni F, Linstedt AD. GM130 and GRASP65-dependent lateral cisternal fusion allows uniform Golgi-enzyme distribution. Nat Cell Biol. 2006 Mar;8(3):238-48. Epub 2006 Feb 19. PMID:16489344 doi:http://dx.doi.org/10.1038/ncb1366
  2. ↑ Marra P, Salvatore L, Mironov A Jr, Di Campli A, Di Tullio G, Trucco A, Beznoussenko G, Mironov A, De Matteis MA. The biogenesis of the Golgi ribbon: the roles of membrane input from the ER and of GM130. Mol Biol Cell. 2007 May;18(5):1595-608. Epub 2007 Feb 21. PMID:17314401 doi:http://dx.doi.org/10.1091/mbc.E06-10-0886
  3. ↑ Kodani A, Sutterlin C. The Golgi protein GM130 regulates centrosome morphology and function. Mol Biol Cell. 2008 Feb;19(2):745-53. Epub 2007 Nov 28. PMID:18045989 doi:http://dx.doi.org/10.1091/mbc.E07-08-0847
  4. ↑ Kodani A, Kristensen I, Huang L, Sutterlin C. GM130-dependent control of Cdc42 activity at the Golgi regulates centrosome organization. Mol Biol Cell. 2009 Feb;20(4):1192-200. doi: 10.1091/mbc.E08-08-0834. Epub 2008, Dec 24. PMID:19109421 doi:http://dx.doi.org/10.1091/mbc.E08-08-0834
  5. ↑ Rivero S, Cardenas J, Bornens M, Rios RM. Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130. EMBO J. 2009 Apr 22;28(8):1016-28. doi: 10.1038/emboj.2009.47. Epub 2009 Feb 26. PMID:19242490 doi:http://dx.doi.org/10.1038/emboj.2009.47
  6. ↑ Wei JH, Zhang ZC, Wynn RM, Seemann J. GM130 Regulates Golgi-Derived Spindle Assembly by Activating TPX2 and Capturing Microtubules. Cell. 2015 Jul 16;162(2):287-99. doi: 10.1016/j.cell.2015.06.014. Epub 2015 Jul, 9. PMID:26165940 doi:http://dx.doi.org/10.1016/j.cell.2015.06.014
  7. ↑ Chang CC, Chen CJ, Grauffel C, Pien YC, Lim C, Tsai SY, Hsia KC. Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-alpha. Nat Commun. 2019 Sep 20;10(1):4307. doi: 10.1038/s41467-019-12207-4. PMID:31541088 doi:http://dx.doi.org/10.1038/s41467-019-12207-4

Contents


PDB ID 6iwa

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