Positioning-dependent bidirectional NELL2 signaling in the brain

Abstract

NELL2 is a secreting neuropeptide and thus believed to be an extracellular signaling molecule with an autocrine, paracrine, and/or endocrine nature. At the same time, NELL2 also possesses the ability to modify ER-initiated intracellular signaling pathways. A striking finding from us and other groups is that the outcome of NELL2 signaling is dependent on the site of NELL2 action: the effects of intracellular NELL2 signaling in terms of downstream gene expression and/or synaptic reorganization could be reversed by the NELL2 signaling initiated extracellularly.