1.N.5.  The Endoplasmic Reticulum (ER) Fusion GTPase, Atlastin (Atlastin) Family

Shape changes and topological remodeling of membranes are essential for the identity of organelles and membrane trafficking. Although all cellular membranes have common features, membranes of different organelles create unique environments that support specialized biological functions. The endoplasmic reticulum (ER) is a prime example of this specialization, as its lipid bilayer forms an interconnected system of cisternae, vesicles, and tubules, providing a highly compartmentalized structure for a multitude of biochemical processes. A variety of peripheral and integral membrane proteins that facilitate membrane curvature generation, fission, and/or fusion have been identified. Among these, the dynamin-related proteins (DRPs) have emerged as key players. McNew et al. 2013 reviewed advances in the functional and molecular understanding of fusion DRPs, exemplified by atlastin, an ER-resident DRP that controls ER structure, function, and signaling.

The endoplasmic reticulum (ER) membrane forms an elaborate network of tubules and sheets that is continuously remodeled. This dynamic behavior requires membrane fusion that is mediated by dynamin-like GTPases: the atlastins in metazoans and Sey1p and related proteins in yeast and plants. Crystal structures of the cytosolic domains of these membrane proteins and biochemical experiments allow them to be integrated into a model that explains many aspects of the molecular mechanism by which these membrane-bound GTPases mediate membrane fusion (Hu and Rapoport 2016). 

 


 

References:

Hu, J. and T.A. Rapoport. (2016). Fusion of the endoplasmic reticulum by membrane-bound GTPases. Semin Cell Dev Biol 60: 105-111.
Hu, J., Y. Shibata, P.P. Zhu, C. Voss, N. Rismanchi, W.A. Prinz, T.A. Rapoport, and C. Blackstone. (2009). A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell 138: 549-561.
Lee, M., S.K. Paik, M.J. Lee, Y.J. Kim, S. Kim, M. Nahm, S.J. Oh, H.M. Kim, J. Yim, C.J. Lee, Y.C. Bae, and S. Lee. (2009). Drosophila Atlastin regulates the stability of muscle microtubules and is required for synapse development. Dev Biol 330: 250-262.
Lee, M., Y. Moon, S. Lee, C. Lee, and Y. Jun. (2019). Ergosterol interacts with Sey1p to promote atlastin-mediated endoplasmic reticulum membrane fusion in Saccharomyces cerevisiae. FASEB J. 33: 3590-3600.
McNew, J.A., H. Sondermann, T. Lee, M. Stern, and F. Brandizzi. (2013). GTP-dependent membrane fusion. Annu. Rev. Cell Dev. Biol. 29: 529-550.
Orso, G., D. Pendin, S. Liu, J. Tosetto, T.J. Moss, J.E. Faust, M. Micaroni, A. Egorova, A. Martinuzzi, J.A. McNew, and A. Daga. (2009). Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin. Nature 460: 978-983.
Examples:

TC#NameOrganismal TypeExample
1.N.5.1.1

Atlastin 1, ALT1, of 558 aas and 2 closely packed C-terminal TMSs (McNew et al. 2013).

Atlastin 1 of Homo sapiens

 
1.N.5.1.2

Atlastin of 541 aas and 2 TMSs near the C-terminus of the protein.  It is a GTPase, tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes (Orso et al. 2009). It functions in endoplasmic reticulum tubular network biogenesis and may also regulate microtubule polymerization and Golgi biogenesis. It is required for dopaminergic neurons survival and the growth of muscles and synapses at neuromuscular junctions (Lee et al. 2009).

Alastin of Drosophila melanogaster (Fruit fly)

 
1.N.5.1.3

Atlastin of 968 aas and 1 or 2 C-terminal TMSs.

Atlastine of Blastocystis sp.

 
1.N.5.1.4

Atlastin-1-like isoform X2of 270 aas and 2 TMSs.

ATL1 of Varroa jacobsoni

 
1.N.5.1.5

Atlastin homologue of 602 aas and 1 putative N-terminal TMS and 3 C-terminal TMSs.

Putative Atlastin of Arabidopsis thaliana

 
1.N.5.1.6

Sey1 of 776 aas and 2 C-terminal TMSs, possibly with 1 or 2 N-terminal TMS(s).  It cooperates with the reticulon proteins RTN1 and RTN2 (see TC family 8.A.102) and the tubule-shaping DP1 family protein YOP1 to generate and maintain the structure of the tubular endoplasmic reticulum network. Has GTPase activity, which is required for its function in ER membrane fusion and reorganization (Hu et al. 2009; Hu and Rapoport 2016). Ergosterol interacts with Sey1p to promote atlastin-mediated endoplasmic reticulum membrane fusion (Lee et al. 2019).

 

Sey1 of Saccharomyces cerevisiae (Baker's yeast)