High impact information on alpha-Adaptin

• Rapid flow of information in the nervous system involves presynaptic vesicle recycling by clathrin-mediated endocytosis, an event triggered by the alpha-adaptin-containing AP2 complex [1].
• Our results suggest an alpha-adaptin-dependent control of the vesicle cycle that maintains the balance between the amount of vesicle- and surface-associated membranes [1].
• Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet [2].
• They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ubiquitin ligases, which target proteins for proteasome-mediated degradation [3].
• Specifically, we show that alpha-adaptin and Rab11, which function critically in the endocytic pathways of all previously examined animal cells, are localized to neighboring compartments at the posterior pole of stage 8-10 oocytes [4].

Biological context of alpha-Adaptin

• Numb and alpha-Adaptin regulate Sanpodo endocytosis to specify cell fate in Drosophila external sensory organs [5].
• The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila [6].
• At later stages of embryogenesis, alpha-adaptin is expressed in complex and dynamic patterns [7].
• There seem to be at least two Drosophila alpha-adaptin transcripts expressed, plausibly by alternative splicing [7].
• Mammalian alpha-adaptins are encoded by two genes; however, Drosophila alpha-adaptin has a single gene locus, within polytene bands 21C2-C3 on the left arm of the chromosome 2, closely adjacent to the paired homeobox gene aristaless [7].

Anatomical context of alpha-Adaptin

• Rab11 and alpha-adaptin localization occurs in the absence of a polarized microtubule cytoskeleton, i.e. in grk null mutants, but is later reinforced and/or refined by Osk, the localization of which is microtubule dependent [4].
• Eps15 mutants show a decrease in the alpha-Adaptin levels at the larval neuromuscular junction synapse [8].
• Genetic and biochemical studies of interactions with components of the endocytic machinery suggest that Eps15 has an important role in synaptic vesicle recycling and regulates recruitment of alpha-Adaptin [8].
• The cells expressing high levels of alpha-adaptin are known or expected to support high levels of endocytosis; thus, this coated vesicle protein seems to be an excellent marker for endocytic activity [7].
• The BAD1 protein was detected most clearly in plasma membrane coated pits, where it colocalized with alpha-adaptin, although other coated pits were noted which apparently did not contain alpha-adaptin [9].

Associations of alpha-Adaptin with chemical compounds

• Nifurtimox, compound ada and compound 1B were clearly mutagenic and recombinogenic whereas the remaining six compounds were negative [10].

Physical interactions of alpha-Adaptin

• Mutant forms of alpha-Adaptin that no longer bind to Numb fail to localize asymmetrically and cause numb-like defects in asymmetric cell division [6].

Other interactions of alpha-Adaptin

• Sanpodo endocytosis requires alpha-Adaptin, a Numb-binding partner involved in clathrin-mediated endocytosis [5].
• Our results establish numb- and alpha-adaptin-dependent endocytosis of Sanpodo as the mechanism by which Notch is regulated during external sensory organ development [5].
• Epsin consists of an epsin NH(2)-terminal homology (ENTH) domain that promotes the interaction with phospholipids, several AP2 binding sites, two clathrin binding sequences, and several Eps15 homology (EH) domain binding motifs [11].
• The expression patterns of dynamin, detected in the embryo by in situ hybridization methods, are very similar to those reported here for alpha-adaptin reflecting the likely coordinated expression of endocytic components [7].
• The differential interaction of beta with alpha-adaptin and beta' with gamma-adaptin in mammalian cells is likely to depend on the few non-conservative differences between their respective sequences and BAD1 [9].

References