Statistical Laws of Protein Motion in Neuronal Dendritic Trees

• Type of Material: Article
• Authors: Fabio Sartori, Max Planck Institute for Brain Research; Anne-Sophie Hafner, Max Planck Institute for Brain Research; Ali Karimi, Max Planck Institute for Brain Research; Andreas Nold, Max Planck Institute for Brain Research; Yombe Fonkeu, Emory University; Erin M. Schuman, Max Planck Institute for Brain Research; Tatjana Tchumatchenko, Max Planck Institute for Brain Research
• Language: English
• Date: 2020-11-17
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2020.108391
• Title of Journal or Parent Work: Cell Reports
• Volume: 33
• Issue: 7
• Grant/Funding Information: This work was funded by the Max Planck Society and German Research Foundation (CRC 1080 to T.T. and E.M.S). E.M.S. is supported by DFG 902, CRC 1080, and an advanced investigator grant from the European Research Council. A.-S.H. is supported by an EMBO long-term postdoctoral fellowship (ALTF 1095-2015) and the Alexander von Humboldt Foundation (FRA-1184902-HFST-P). A.N. acknowledges support from an add-on scholarship of the Joachim Herz Foundation.
• Keywords: Rall’s rule; branching radii; intracellular diffusion; dendritic morphology; radii optimization; 3D EM neuronal reconstructions
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

Across their dendritic trees, neurons distribute thousands of protein species that are necessary for maintaining synaptic function and plasticity and that need to be produced continuously and trafficked to their final destination. As each dendritic branchpoint splits the protein flow, increasing branchpoints decreases the total protein number downstream. Consequently, a neuron needs to produce more proteins to maintain a minimal protein number at distal synapses. Combining in vitro experiments and a theoretical framework, we show that proteins that diffuse within the cell plasma membrane are, on average, 35% more effective at reaching downstream locations than proteins that diffuse in the cytoplasm. This advantage emerges from a bias for forward motion at branchpoints when proteins diffuse within the plasma membrane. Using 3D electron microscopy (EM) data, we show that pyramidal branching statistics and the diffusion lengths of common proteins fall into a region that minimizes the overall protein need.