γ2 and γ1AP-1 complexes: Different essential functions and regulatory mechanisms in clathrin-dependent protein sorting

gamma 2 adaptin is homologous to gamma 1, but is only expressed in vertebrates while gamma 1 is found in all eukaryotes. We know little about gamma 2 functions and their relation to gamma 1. gamma 1 is an adaptin of the heterotetrameric AP-1 complexes, which sort proteins in and do form clathrin-coated transport vesicles and they also regulate maturation of early endosomes. gamma 1 knockout mice develop only to blastocysts and thus gamma 2 does not compensate gamma 1-deficiency in development. gamma 2 has not been classified as a clathrin-coated vesicle adaptor protein in proteome analyses and functions for monomeric gamma 2 in endosomal protein sorting have been proposed, but adaptin interaction studies suggested formation of heterotetrameric AP-1/gamma 2 complexes. We detected gamma 2 at the trans-Golgi network, on peripheral vesicles and identified gamma 2 clathrin-coated vesicles in mice. Ubiquitous sigma 1A and tissue-specific sigma 1B adaptins bind gamma 2 and gamma 1. sigma 1B knockout in mice does not effect gamma 1/sigma 1A AP-1 levels, but gamma 2/sigma 1A AP-1 levels are increased in brain and adipocytes. Also gamma 2 is essential in development. In zebrafish AP-1/gamma 2 and AP-1/gamma 1 fulfill different, essential functions in brain and the vascular system. (C) 2017 Elsevier GmbH. All rights reserved.