The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module that defines
monomeric adaptor proteins of the epsin family. It is present in the epsin or epsin-related (epsinR) proteins, which are
implicated in the endocytosis and Golgi-to-endosomes protein trafficking, respectively, in other eukaryotic cells. In
Giardia we found a single gene encoding a protein containing an ENTH domain (GlENTHp for G. lamblia ENTH
protein), which localized in the cytosol and, like epsin, was associated with
áAP-2, clathrin, ubiquitin, interacted with
PI3,4,5P3, and was involved in receptor-mediated endocytosis. This protein also bonded
ãAP-1, PI4P, and was
implicated in ER-to-PV trafficking, like epsinR proteins. Alteration of the GlENTHp function affected trophozoite
growth showing an accumulation of dense material in the lysosome-like peripheral vacuoles (PVs), indicating that
GlENTHp might be implicated in the maintenance of the PV homeostasis. When the ENTH protein family was
analyzed in an evolutionary context, it was suggested that the subfamily of epsin proteins was acquired more recently
probably by duplication of the epsinR. In this study, we showed evidence that places GlENTHp at the beginning of
the whole family, summarizing the function of epsin and epsinR and suggesting that GlENTHp might be the epsinR
adaptor from which all the family evolves
