TY - JOUR
T1 - Membrane-associated periodic skeleton is a signaling platform for RTK transactivation in neurons
AU - Zhou, Ruobo
AU - Han, Boran
AU - Xia, Chenglong
AU - Zhuang, Xiaowei
N1 - Funding Information:
We thank H. Babcock and Y. Fu for helping with two-color STORM imaging setup construction and data analysis, K. Xu for providing the software for processing the two-color STORM imaging data, and M. Rasband for providing the adenoviruses expressing shRNA against bII-spectrin. Funding: This work is supported in part by the National Institutes of Health. R.Z. is an HHMI Fellow of the Life Sciences Research Foundation. X.Z. is a Howard Hughes Medical
Publisher Copyright:
© 2019 American Association for the Advancement of Science. All rights reserved.
PY - 2019/8/30
Y1 - 2019/8/30
N2 - 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.
AB - 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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U2 - 10.1126/science.aaw5937
DO - 10.1126/science.aaw5937
M3 - Article
C2 - 31467223
AN - SCOPUS:85071416780
SN - 0036-8075
VL - 365
SP - 929
EP - 934
JO - Science
JF - Science
IS - 6456
ER -