Ligand-Induced Dynamics of Neurotrophin Receptors Investigated by Single-Molecule Imaging Approaches

International Journal of Molecular Sciences

Laura Marchetti¹  Stefano Luin¹  Fulvio Bonsignore¹  Teresa de Nadai²  Fabio Beltram¹  Antonino Cattaneo² 

[1] National Enterprise for nanoScience and nanoTechnology (NEST) Laboratory, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, Pisa I-56127, Italy; E-Mails:;Biology Laboratory (BioSNS), Scuola Normale Superiore and Istituto di Neuroscienze-CNR, via Moruzzi 1, Pisa I-56100, Italy; E-Mail:

关键词: neurotrophin receptors;    nerve growth factor;    single molecule imaging;    single molecule tracking;    single molecule interactions;    binding stoichiometry;    receptor clustering;    membrane trafficking;    receptor internalization;   

DOI  :  10.3390/ijms16011949

来源: mdpi

【 摘 要 】

Neurotrophins are secreted proteins that regulate neuronal development and survival, as well as maintenance and plasticity of the adult nervous system. The biological activity of neurotrophins stems from their binding to two membrane receptor types, the tropomyosin receptor kinase and the p75 neurotrophin receptors (NRs). The intracellular signalling cascades thereby activated have been extensively investigated. Nevertheless, a comprehensive description of the ligand-induced nanoscale details of NRs dynamics and interactions spanning from the initial lateral movements triggered at the plasma membrane to the internalization and transport processes is still missing. Recent advances in high spatio-temporal resolution imaging techniques have yielded new insight on the dynamics of NRs upon ligand binding. Here we discuss requirements, potential and practical implementation of these novel approaches for the study of neurotrophin trafficking and signalling, in the framework of current knowledge available also for other ligand-receptor systems. We shall especially highlight the correlation between the receptor dynamics activated by different neurotrophins and the respective signalling outcome, as recently revealed by single-molecule tracking of NRs in living neuronal cells.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.