Diering Graham H, Numata Masayuki
Department of Neuroscience, Johns Hopkins University School of Medicine Baltimore, MD, USA.
Department of Biochemistry and Molecular Biology, University of British Columbia Vancouver, BC, Canada.
Front Physiol. 2014 Jan 13;4:412. doi: 10.3389/fphys.2013.00412.
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.
神经元前体细胞在发育过程中会伸出多条神经突，其中一条会延伸形成轴突，而其他的则发育为树突。在完全分化的神经元中，对N-甲基-D-天冬氨酸（NMDA）受体进行化学刺激会诱导树突棘的形成，树突棘是从树突伸出的小突起，从而在树突内建立另一层极性。富含神经元的钠/氢交换蛋白NHE5对神经突生长和树突棘形成均有作用。在静息神经元和神经内分泌细胞中，富含神经元的NHE5主要与再循环内体相关，在那里它与神经生长因子（NGF）受体TrkA共定位。NHE5有效地酸化TrkA阳性再循环内体的腔，并调节TrkA的细胞表面靶向，而对NMDA受体的化学刺激会迅速将NHE5募集到树突棘，使树突碱化并下调树突棘的形成。本文讨论了NHE5通过质子在亚细胞区室中的移动在神经元信号传导中的可能作用。
