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Adaptor protein (AP) complexes are heterotetramers that select cargo for inclusion into transport vesicles. Five AP complexes (AP-1 to AP-5) have been described, each with a distinct localisation and function. Furthermore, patients with a range of disorders, particularly involving the nervous system, have now been identified with mutations in each of the AP complexes. In many cases this has been correlated with aberrantly localised membrane proteins. In this Cell Science at a Glance article and the accompanying poster, we summarize what is known about the five AP complexes and discuss how this helps to explain the clinical features of the different genetic disorders., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

There are two alpha-adaptin genes, alpha A and alpha C, which in brain encode proteins of of M(r) 108 x 10(3) and 104 x 10(3), respectively. Although both mRNAs can be detected on northern blots of brain and liver, the higher molecular mass polypeptide can only be detected on western blots of brain. Here we explain these observations by showing that alpha A is alternatively spliced and that the protein product in most tissues is different from the one expressed in brain in that it is missing 21 amino acids within the hinge region, giving it a similar mobility to that of alpha C. Monospecific antibodies were raised against the various alpha-adaptin isoforms and used to compare their distribution in cells and tissues. Both alpha A and alpha c are co-assembled into the same coated pits, and the larger isoform of alpha A is co-assembled with the smaller isoforms of alpha-adaptin, both in cells that naturally express it an in transfected cells. Examination of brain and spinal cord sections, labelled either for the larger isoform of alpha A or for alpha C, reveals that that the two are to some extent differentially distributed, consistent with previous in situ hybridisation studies. This finding, combined with the observation that there is considerable variability in the relative expression of the two isoforms in different tissues, indicates that the two genes are switched on in response to different stimuli. Moreover, the larger isoform of alpha A appears to be more efficiently concentrated in the nerve terminals than alpha C, which is found not only at the terminals but also diffusely distributed in the cell bodies and dendrites. This suggests that alpha C may play more of a role in the recycling of membrane components throughout the cell.