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).
The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. Wisesa et al. 2019 reported TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains of TMCC3. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. Thus, TMCC3 localizes at the three-way junctions for the proper tubular ER network (Wisesa et al. 2019).
There are 18 TaATLas from wheat (Triticum aestivum), and they are regulated by light, hormones, and stress signals (Chen et al. 2024). Functional assays revealed that TaATLa6 transports glutamine (Gln), glutamate (Glu), and aspartate (Asp) in yeast. In contrast, TaATLa4 specifically transports Gln and Asp. Furthermore, TaATLas exhibits diverse gene expression patterns, with TaATLa4-7D enhancing yeast heat tolerance in a heterologous expression system, indicating its potential role in adapting to environmental stress by regulating amino acid transport and distribution. This study sheds light on the functional roles of TaATLa genes, with implications for improving nitrogen use in wheat and other crop species (Chen et al. 2024).
References:
Atlastin 1, ALT1, of 558 aas and 2 closely packed C-terminal TMSs (McNew et al. 2013).
Atlastin 1 of Homo sapiens
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)
Atlastin of 968 aas and 1 or 2 TMSs, possibly one N-terminal TMS and one C-terminal TMS.
Atlastine of Blastocystis sp.
Atlastin-1-like isoform X2 of 270 aas and 2 TMSs, one at residue 140 and one at residue 180.
ATL1 of Varroa jacobsoni
Atlastin homologue of 602 aas and 1 putative N-terminal TMS and 3 C-terminal TMSs.
Putative Atlastin of Arabidopsis thaliana
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)
Atlastin-3, ATL3, of 541 aas and 3 TMSs, 2 near the C-terminus, and possibly 1 near the N-terminus. It is a reticulophagy receptor (Yang and Klionsky 2020).
ATL3 of Homo sapiens