The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.

Centrosomes are organelles that nucleate microtubules via the activity of gamma-tubulin ring complexes (γ-TuRC). In the developing brain, centrosome integrity is central to the progression of the neural progenitor cell cycle, and its loss leads to microcephaly. We show that NPCs maintain centrosome integrity via the endocytic adaptor protein complex-2 (AP-2).

Brain-specific functions of the endocytic machinery.

Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. In a broad sense, endocytosis is accomplished through either constitutive or ligand-induced invagination of the plasma membrane, which results in the formation of the plasma membrane-retrieved endocytic vesicles, which can either be sent for degradation to the lysosomes or recycled back to the PM. This additional function of endocytosis in membrane retrieval has been adopted by excitable cells, such as neurons, for membrane equilibrium maintenance at synapses.

Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-α (IFN-α) potentiates immune responses against viral pathogens that induce toll-like receptor-3 (TLR3) activation but evokes severe major depressive disorder in humans by mechanisms that remain insufficiently described. By using a previously established mouse model of depression induced by combined delivery of IFN-α and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-α and poly(I:C) reduce apical dendritic spine density in the hippocampal CA1 area ex vivo via mechanisms involving decreased TrkB signaling.

AP-2 reduces amyloidogenesis by promoting BACE1 trafficking and degradation in neurons.

Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme 1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathological hallmark of Alzheimer's disease (AD). Despite decades of research, mechanisms of amyloidogenic APP processing remain highly controversial. Here, we show that in neurons, APP processing and Aβ production are controlled by the protein complex-2 (AP-2), an endocytic adaptor known to be required for APP endocytosis.