Trends in Biochemical Sciences
Longins and their longin domains: regulated SNAREs and multifunctional SNARE regulators
Section snippets
Molecular organization and functions of LDs
Figure 1 compares the domain architecture of longins to that of other SNAREs. Both longins and syntaxins have N-terminal domains (NTDs) that can downregulate membrane fusion 15, 16, 17. When the 3D structures of the NTDs of the longins Ykt6 and Sec22b were solved, however, the LD was found to show a conserved profilin-like fold that differed considerably from that of the NTD of syntaxins 18, 19 (Box 1).
Intramolecular binding of the NTD of neuronal syntaxin to its SNARE motif mediates the
TI-VAMP
Depending on the type of cell, TI-VAMP has been found to interact in vivo with several t-SNARE heavy chains (plasmalemmal syntaxin 1, 3 and 4, and late endosomal syntaxin 7) and light chains (SNAP-23, -25 and -29, syntaxins 6, 8 and 10, and Vti1b), but not with syntaxin 16 (in the Golgi) or syntaxin 13 (in early endosomes) 11, 17, 22, 29, 33, 34, 35, 36. Although physiological roles for all of these associations remain to be determined, these interactions clearly indicate that TI-VAMP is
Sec22 and Ykt6
The proteome of yeast Saccharomyces cerevisiae contains five R-SNAREs: its two ‘brevins’ 7, 8 (Snc1 and Snc2) function in trafficking to the cell surface, both within the endosomal system and between endosomes and the Golgi [50]; Nyv1 is the largest of the five R-SNAREs and the least similar to the other four [51]; and the two longins (Sec22 and Ykt6) are evolutionarily conserved proteins, but only Ykt6 is essential [14].
Distribution and domain variation
Although longins represent the most conserved and widely distributed R-SNAREs in terms of both their LDs and their SNARE motifs 7, 10, a comparison of the R-SNARE proteomic complements from model eukaryotes with completely sequenced genomes demonstrates that the longin subfamilies show different distributions and varying numbers of members among taxa (Table 1).
The Sec22 and Ykt6 longins have an apparently homogeneous distribution and number of genes, whereas the TI-VAMP longins and brevins are
Concluding remarks
The SNARE family has remained mostly unchanged in yeast, flies and worms, but has significantly increased in the number of representatives in mammals [6] and plants [9]. These features suggest that multicellular organisms, first, do not have an inherently more complex secretory pathway and, second, use additional SNAREs for the tissue-specific specialization of membrane trafficking [6]. The possibility that longins and brevins might have different roles in differentiation, development and
Acknowledgements
This manuscript is dedicated to the memory of Giuliana Ferrarone. V.R. and M.V. are supported, respectively, by a research associate and a postdoctoral fellowship funded by the University of Padua. L.E.P.D. is a recipient of a predoctoral fellowship of the Boehringer Ingelheim Fonds. D.K.B.'s laboratory is supported by the Research Grants Council of Hong Kong; C.U.'s laboratory by the DFG, the SFB638, the Fonds der Chemischen Industrie and the EMBO young investigator programme; M.D.E.'s
References (82)
A model for structural similarity between different SNARE complexes based on sequence relationships
Trends Cell Biol.
(1998)Longins: a new evolutionary conserved VAMP family sharing a novel SNARE domain
Trends Biochem. Sci.
(2001)Control of eukaryotic membrane fusion by N-terminal domains of SNARE proteins
Biochim. Biophys. Acta
(2003)A new catch in the SNARE
Trends Plant Sci.
(2004)VAMP subfamilies identified by specific R-SNARE motifs
Biol. Cell
(2004)Seven novel mammalian SNARE proteins localize to distinct membrane compartments
J. Biol. Chem.
(1998)The synaptobrevin-related domains of Bos1p and Sec22p bind to the syntaxin-like region of Sed5p
J. Biol. Chem.
(1997)Ykt6p, a prenylated SNARE essential for endoplasmic reticulum–Golgi transport
J. Biol. Chem.
(1997)A novel SNARE N-terminal domain revealed by the crystal structure of Sec22b
J. Biol. Chem.
(2001)- et al.
Vesicle trafficking: pleasure and pain from SM genes
Trends Cell Biol.
(2003)
SNARE selectivity of the COPII coat
Cell
The GAF domain: an evolutionary link between diverse phototransducing proteins
Trends Biochem. Sci.
Identification of SNAREs involved in Synaptotagmin VII-regulated lysosomal exocytosis
J. Biol. Chem.
Syntaxin 7 complexes with mouse Vps10p tail interactor 1b, syntaxin 6, vesicle-associated membrane protein (VAMP)8, and VAMP7 in b16 melanoma cells
J. Biol. Chem.
Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes
Cell
Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes
Biochem. Biophys. Res. Commun.
The cell outgrowth secretory endosome (COSE): a specialized compartment involved in neuronal morphogenesis
Biol. Cell.
Genetic interactions with the yeast Q-SNARE VTI1 reveal novel functions for the R-SNARE YKT6
J. Biol. Chem.
Sec22p export from the endoplasmic reticulum is independent of SNARE pairing
J. Biol. Chem.
Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a late stage in endoplasmic reticulum–Golgi transport
J. Biol. Chem.
Hsec22c: a homolog of yeast Sec22p and mammalian rsec22a and msec22b/ERS-24
Biochem. Biophys. Res. Commun.
The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation and contains a non-canonical splice site
Gene
SNARE complexes – is there sufficient complexity for vesicle targeting specificity?
Trends Biochem. Sci.
Crystal structure of SEDL and its implications for a genetic disease spondyloepiphyseal dysplasia tarda
J. Biol. Chem.
Human wild-type SEDL protein functionally complements yeast Trs20p but some naturally occurring SEDL mutants do not
Gene
Adaptable adaptors for coated vesicles
Trends Cell Biol.
Molecular architecture and functional model of the endocytic AP2 complex
Cell
Tetanus neurotoxin-insensitive vesicle-associated membrane protein localizes to a presynaptic membrane compartment in selected terminal subsets of the rat brain
Neuroscience
SNARE protein structure and function
Annu. Rev. Cell Dev. Biol.
Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
Nature
Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs
Proc. Natl. Acad. Sci. U. S. A.
Exocytosis requires asymmetry in the central layer of the SNARE complex
EMBO J.
A genomic perspective on membrane compartment organization
Nature
A novel tetanus neurotoxin-insensitive vesicle-associated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells
Mol. Biol. Cell
Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p
Nat. Struct. Biol.
Rapid and efficient fusion of phospholipid vesicles by the α-helical core of a SNARE complex in the absence of an N-terminal regulatory domain
Proc. Natl. Acad. Sci. U. S. A.
Role of tetanus neurotoxin insensitive vesicle-associated membrane protein (TI-VAMP) in vesicular transport mediating neurite outgrowth
J. Cell Biol.
An autoinhibitory mechanism for nonsyntaxin SNARE proteins revealed by the structure of Ykt6p
Science
A dual mechanism controlling the localization and function of exocytic v-SNAREs
Proc. Natl. Acad. Sci. U. S. A.
The PAS fold. A redefinition of the PAS domain based upon structural prediction
Eur. J. Biochem.
Profilin II is alternatively spliced, resulting in profilin isoforms that are differentially expressed and have distinct biochemical properties
Mol. Cell. Biol.
Cited by (127)
Vesicle fusion induced by zwitterionic amphiphilic channels
2024, Chinese Chemical LettersComparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis
2023, Journal of Biological ChemistryDifferent conformational dynamics of SNARE protein Ykt6 among yeast and mammals
2023, Journal of Biological ChemistryFLCN regulates transferrin receptor 1 transport and iron homeostasis
2021, Journal of Biological ChemistryTemperament gene inheritance
2020, Meta Gene