GABARAPL1 (GEC1) associates with autophagic vesicles

Abstract

Gabarapl1 (gec1) was first described as an estrogen regulated gene which shares a high sequence homology with the gabarap gene. We previously demonstrated that GABARAPL1, like GABARAP, interacts with the GABAA receptor and tubulin and promotes tubulin polymerization. Previous work has demonstrated that the GABARAP family members (GABARAP, LC3, GATE-16 and Atg8) are not only involved in the transport of proteins or vesicles but are also implicated in various mechanisms such as autophagy, cell death, cell proliferation and tumor progression. We therefore asked whether GABARAPL1 might also play a role in autophagy. First, we showed that GABARAPL1 is cleaved at glycine 116, a residue which is conserved in other members of the family. We also demonstrated that GABARAPL1 is linked to phospholipids, delipidated by Atg4B, associated with intracellular membranes and accumulated in intracellular vesicles after inhibition of lysosomal activity. Finally, we showed that GABARAPL1 partially colocalizes with LC3 or Lysotracker green in intracellular vesicles. Taken together, our results demonstrate that GABARAPL1 associates with autophagic vesicles.

GABARAPL1 (GEC1): Original or copycat?

“…1). 11,12 In addition to their sequence similarity, the crystal structures of GABARAP, [13][14][15][16][17] GATE-16, 6 LC3, 18 and…”

“…These studies have shown that the cellular distribution of GABARAPL1 is highly variable, including the cytoplasm, Golgi complex, endoplasmic reticulum or the plasma membrane, but with a common feature, a staining linked to intracytoplasmic vesicles that can partially colocalize with autophagosomes or lysosomes. 45,46,48,49 Although these experiments make it possible to determine the expression pattern of exogenous GABARAPL1, the cellular distribution of endogenous GABARAPL1 remains to be confirmed.…”

“…63 Recently, Gabarapl1 has been described as a new marker of autophagosomes 48 and can be cleaved by Atg4B in vitro, a maturation step described to be inhibited in Atg4B -/-mice. 48,64,65 The loss of the maturation of the Gabarap family members by Atg4B in this in vivo model leads to balance disorders owing to a loss of autophagic function within the inner ear.…”

GABARAPL1 antibodies: Target one protein, get one free!

“…2B, lane 3), producing only one signal corresponding to the with a higher percentage of acrylamide in the gel and a longer migration time. 3,13 Immunohistological analysis of the endogenous proteins, however, does not provide an easy alternative to the necessity of specific antibodies. Indeed, many researchers have encountered this problem of cross-reactivity with both their 'homemade' and commercially bought antisera and purified antibodies raised against either GABARAPL1 or GABARAP.…”

“…3 The exact role of GABARAPL1 in intracellular transport and autophagy, however, is still unanswered, and will require further studies to address the remaining uncertainties. As with any experiment, the proper tools are critical to its success.…”