Endosomal pH in neuronal signaling and synaptic transmission: role of Na(+)/H(+) exchanger NHE5.
Neuronal precursor cells extend multiple neurites during development, one of which extends to form an axon whereas others develop into dendrites. Chemical stimulation of N-methyl D-aspartate (NMDA) receptor in fully-differentiated neurons induces projection of dendritic spines, small spikes protruding from dendrites, thereby establishing another layer of polarity within the dendrite. Neuron-enriched Na(+)/H(+) exchanger NHE5 contributes to both neurite growth and dendritic spine formation. In resting neurons and neuro-endocrine cells, neuron-enriched NHE5 is predominantly associated with recycling endosomes where it colocalizes with nerve growth factor (NGF) receptor TrkA. NHE5 potently acidifies the lumen of TrkA-positive recycling endosomes and regulates cell-surface targeting of TrkA, whereas chemical stimulation of NMDA receptors rapidly recruits NHE5 to dendritic spines, alkalinizes dendrites and down-regulates the dendritic spine formation. Possible roles of NHE5 in neuronal signaling via proton movement in subcellular compartments are discussed.
Department of Neuroscience, Johns Hopkins University School of Medicine Baltimore, MD, USA.
Graham H
GH
Diering
Department of Biochemistry and Molecular Biology, University of British Columbia Vancouver, BC, Canada.
Masayuki
M
Numata
NMDA receptor; Trk receptors; dendritic spines; endocytic recycling; neurites; neurotrophins; protons; signaling endosomes