Protein translocation into dendrites: implication of glia-derived angiotensins in noradrenergic brainstem neurons

Noradrenaline (NA) released by dendrites of locus coeruleus (LC) neurons controls LC neuron activity, and hence, NA released from noradrenergic fibers in terminal fields. NA synthesis is dependent on tyrosine hydroxylase (TH), whose dendritic presence is controlled precisely in LC neurons during postnatal development. However, the mechanisms controlling specifically dendritic sorting of TH without affecting its axonal transport remained to be elucidated. Here, by using transgenic rats with astrocyte-directed depletion of angiotensinogen, we show that dendritic but not axonal TH protein sorting is initiated after weaning by cerebral angiotensins in LC neurons, but not in dopaminergic neurons of the substantia nigra (SN). Cerebral angiotensins trigger dendritic translocation of TH protein by stimulating phosphorylation of the myristoylated alanine-rich C kinase substrate (MARCKS), known to facilitate macromolecule export from the soma. Protein trafficking within either axons or dendrites of LC neurons is thus controlled by specialized mechanisms, some having a glial origin.