Data for: Human atlastin-3 is a constitutive ER membrane fusion catalyst (phylogenetic and sequence analysis)

Homotypic membrane fusion catalyzed by the atlastin (ATL) GTPase sustains
the branched endoplasmic reticulum (ER) network in metazoans. Our recent
discovery that two of the three human ATL paralogs (ATL1/2) are
C-terminally autoinhibited implied that relief of autoinhibition would be
integral to the ATL fusion mechanism. An alternative hypothesis is that
the third paralog ATL3 promotes constitutive ER fusion with relief of
ATL1/2 autoinhibition used conditionally. However, published studies
suggest ATL3 is a weak fusogen at best. Contrary to expectations, we
demonstrate here that purified human ATL3 catalyzes efficient membrane
fusion in vitro and is sufficient to sustain the ER network in triple
knockout cells. Strikingly, ATL3 lacks any detectable C-terminal
autoinhibition, like the invertebrate Drosophila ATL ortholog.
Phylogenetic analysis of ATL C-termini indicates that C-terminal
autoinhibition is a recent evolutionary innovation. We suggest that ATL3
is a constitutive ER fusion catalyst and that ATL1/2 autoinhibition likely
evolved in vertebrates as a means of upregulating ER fusion activity on
demand.