Physiological Roles of Clathrin Adaptor AP Complexes: Lessons from Mutant Animals

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Abstract
Clathrin-associated adaptor protein (AP) complexes play a key role in the transport of proteins, by regulating the formation of transport vesicles as well as cargo selection, between organelles of the post-Golgi network, namely, the trans-Golgi network (TGN), endosomes, lysosomes and the plasma membrane. Evidence has been accumulating for the physiological importance of AP complexes. Deficiency in AP-1A or AP-2 results in embryonic lethality in mice, indicating that these AP complexes are essential for normal development of embryos in mammals. In contrast, mutations in the genes encoding subunits of AP-3A cause an autosomal recessive disorder, Hermansky-Pudlak syndrome in human and its disease models in mice. Knockout mice for the neuron-specific AP-3B suffer from epileptic seizure. Further studies on the physiological and pathological aspects of AP complexes will not only be beneficial for better understanding of developmental biology and medical sciences, but also deepen our insight into the molecular mechanisms of vesicular traffic.

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