A dynamic signaling scaffold
In neurons, many cellular processes are regulated by receptor tyrosine kinases (RTKs), cell surface receptors whose activation can depend on other signaling pathways. Zhou et al. used super-resolution imaging to visualize colocalization of signaling proteins on the membrane-associated periodic skeleton (MPS) that is formed by actin, spectrin, and related molecules in the axons and dendrites of neurons. The colocalization of signaling proteins in different pathways leads to transactivation of RTK, which initiates intracellular signaling. In a negative feedback loop, the downstream signaling in turn leads to degradation of the MPS. Thus, the MPS is a dynamically regulated platform that coordinates signal transduction in neurons.
Science, this issue p. 929
Abstract
Actin, spectrin, and related molecules form a membrane-associated periodic skeleton (MPS) in neurons. The function of the MPS, however, remains poorly understood. Using super-resolution imaging, we observed that G protein–coupled receptors (GPCRs), cell adhesion molecules (CAMs), receptor tyrosine kinases (RTKs), and related signaling molecules were recruited to the MPS in response to extracellular stimuli, resulting in colocalization of these molecules and RTK transactivation by GPCRs and CAMs, giving rise to extracellular signal–regulated kinase (ERK) signaling. Disruption of the MPS prevented such molecular colocalizations and downstream ERK signaling. ERK signaling in turn caused calpain-dependent MPS degradation, providing a negative feedback that modulates signaling strength. These results reveal an important functional role of the MPS and establish it as a dynamically regulated platform for GPCR- and CAM-mediated RTK signaling.
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