After dendritic proteins are sorted into a specific vesicle population, additional machinery must be recruited to ensure that these Selleck Akt inhibitor vesicles are transported only into dendrites and that they deliver their cargoes only at the correct sites. Two recent studies using novel experimental strategies have identified the kinesins and myosins

that associate preferentially with TfR-containing vesicles (Al-Bassam et al., 2012; Jenkins et al., 2012). Could AP-1A play a role in recruiting such components to dendritic vesicles? Consistent with this idea, recent work shows that the kinesin KIF13A, a known binding partner of the β subunit of AP-1 (Nakagawa et al., 2000), is implicated in the transport of TfR vesicles (Jenkins et al., 2012). Finally,

what regulates axonal protein sorting? The trafficking pathways that underlie axonal polarity remain the subject of active investigation, and no clear consensus has yet emerged concerning the nature or significance of sorting signals in axonally polarized proteins (Lasiecka et al., 2009). The strategy developed by Farías et al.—using a detailed analysis of the binding between sorting motifs and adaptors to design reagents to manipulate sorting in living cells—could also be used to elucidate the machinery that directs axonal sorting. “
“Neurons come in two flavors: Venetoclax in vivo excitatory and inhibitory. Because excitatory neurons usually outnumber inhibitory neurons in most brain regions, it’s not surprising that we know more about excitation than inhibition. This extends to our understanding of how inhibition regulates dendritic excitability. Although originally thought of as passive integrators of incoming synaptic inputs, we now know that dendrites express a range of voltage-gated channels and, as a result, can perform a variety of active forms of synaptic integration. This includes the generation of dendritic “spikes”—all-or-none, active

responses initiated in localized dendritic regions or branches following the activation of dendritic voltage-gated sodium and/or Oxymatrine calcium channels, as well as NMDA receptors, which derive their voltage dependence via external magnesium block. These active forms of dendritic integration have been studied in great detail over the last two decades, primarily due to advances that have allowed dendrites of neurons to be investigated directly using either electrophysiological or imaging techniques. What has been missing from the puzzle is an understanding of how this dendritic excitability is regulated by inhibition. In the current issue of Neuron, Müller and colleagues (2012) investigate the role of inhibition in regulating dendritic excitability in hippocampal CA1 pyramidal neurons.