Avital Rodal

Avital Rodal, Biology faculty member, Brandeis UniversityAssociate Professor of Biology

Research Description

Endosomal Membrane Traffic in Neurons

Our lab is focused on understanding how neurons set up elaborate structures that are tailored to send and receive electrical signals over large distances and through complex networks of connections. Neurons undergo dynamic structural changes in response to external growth cues during development as well as learning and memory, and die back in the absence of positive growth cues. These growth cues are received at the cell surface and are trafficked into the cell via a network of membrane-bound compartments called endosomes. However, we still do not understand the identity of the internal compartments from which growth cues signal, the special properties of those compartments that enable signaling to occur, and ultimately how the hundreds of proteins that make up the membrane traffic machinery can themselves be regulated to tune signaling up or down. These receptor trafficking events are implicated in neuronal diseases ranging from neurodegenerative disease to mental retardation and addiction, underlining the health importance of understanding how signal transduction is modulated by intracellular membrane traffic in neurons. 

We use a combination of biochemistry, genetics, and live imaging, primarily in the fruit fly nervous system (but also in mammalian cultured cells) to unravel the molecular mechanisms by which the traffic of signaling receptors that control the architecture of synapses is regulated by interacting networks of membrane remodeling proteins. We are also exploring the connection between neurodegenerative disease phenotypes and these membrane trafficking  pathways, using genetics and live imaging to manipulate and visualize sub-cellular neuronal trafficking events in established Drosophila models of ALS and Alzheimer's Disease.

Fluorescence microscopy images of membrane trafficking and remodeling events in neurons, in cells in culture, and in purified systems.
Fluorescence microscopy images of membrane trafficking and remodeling events in neurons, in cells in culture, and in purified systems.

Selected Publications

  • Blanchette CR, Scalera AL, Harris KP, Zhao Z, Koles K, Yeh A, Apiki JK, Stewart BA,  Rodal AA. Local regulation of extracellular vesicle traffic by the synaptic endocytic machinery. bioRxiv 2021.08.04.454987.
  • Del Signore SJ, Kelley CF, Messelaar EM, Lemos T, Marchan MF, Ermanoska B, Mund M, Fai TG, Kaksonen M, Rodal AA. An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis. Elife. 2021 Jul 29;10:e69597. doi: 10.7554/eLife.69597.
  • Rylie B. Walsh, Agata N. Becalska, Matthew J. Zunitch, Tania Lemos, Erica C. Dresselhaus, So Min Lee, ShiYu Wang, Berith Isaac, Anna Yeh, Kate Koles, Avital A. Rodal.  Opposing functions for retromer and Rab11 in extracellular vesicle cargo traffic at presynaptic terminalsJournal of Cell Biology. 2021 May 21.
  • Herzog JJ, Xu W, Deshpande M, Rahman R, Suib H, Rodal AA, Rosbash M, Paradis S. TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression. Proc Natl Acad Sci U S A. 2020 May 11; pii: 201917038. doi: 10.1073/pnas.1917038117.
  • Blanchette CR, and Rodal AA. Mechanisms for biogenesis and release of neuronal extracellular vesicles. Current Opinion in Neurobiology. Volume 63, August 2020, Pages 104-110.
  • Ye H, Ojelade SA, Li-Kroeger D, Zuo Z, Wang L, Li Y, Gu JYJ, Tepass U, Rodal AA, Bellen HJ, Shulman JM. Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain. Elife. 2020 Apr 14;9. pii: e51977. doi: 10.7554/eLife.51977. 
  • Nguyen DN, Redman RL, Horiya S, Bailey JK, Xu B, Stanfield RL, Temme JS, LaBranche CC, Wang S, Rodal AA, Montefiori DC, Wilson IA, Krauss IJ. The Impact of Sustained Immunization Regimens on the Antibody Response to Oligomannose Glycans. ACS Chem Biol. 2020 Mar 20;15(3):789-798. doi: 10.1021/acschembio.0c00053.
  • Zuraw-Weston S, Wood DA, Torres IK, Lee Y, Wang LS, Jiang Z, Lázaro GR, Wang S, Rodal AA, Hagan MF, Rotello VM, Dinsmore AD. Nanoparticles binding to lipid membranes: from vesicle-based gels to vesicle tubulation and destruction. Nanoscale. 2019 Oct 10;11(39):18464-18474. doi: 10.1039/c9nr06570a.
  • Wang S, Zhao Z, Rodal AA.  Higher-order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes. J Cell Biol. 2019 Aug 5. pii: jcb.201811074. doi: 10.1083/jcb.201811074.
  • Del Signore SJ, Rodal AA. The enemy of my enemy: PTEN and PLCXD collude to fight endosomal PtdIns(4,5)P2. J Cell Biol. 2019 Jul 1. pii: jcb.201906022. doi: 10.1083/jcb.201906022.
  • Wang H, Feng Z, Del Signore SJ, Rodal AA, Xu B. Active Probes for Imaging Membrane Dynamics of Live Cells with High Spatial and Temporal Resolution over Extended Time Scales and Areas. J Am Chem Soc. 2018 Mar 14;140(10):3505-3509. doi: 10.1021/jacs.7b13307. 
  • Zhou J, Du X, Berciu C, Del Signore SJ, Chen X, Yamagata N, Rodal AA, Nicastro D, Xu B. Cellular Uptake of A Taurine-Modified, Ester Bond-Decorated D-Peptide Derivative via Dynamin-Based Endocytosis and Macropinocytosis.  Mol Ther. 2018 Feb 7;26(2):648-658. doi: 10.1016/j.ymthe.2017.11.020.
  • Herzog JJ, Deshpande M, Shapiro L, Rodal AA, Paradis S. TDP-43 misexpression causes defects in dendritic growth. Sci Rep. 2017 Nov 15. doi:10.1038/s41598-017-15914-4.
  • Wang H, Shi J, Feng Z, Zhou R, Wang S, Rodal AA, Xu B. An in situ Dynamic Continuum of Supramolecular Phosphoglycopeptides Enables Formation of 3D Cell Spheroids. Angew Chem Int Ed Engl. 2017 Dec 18;56(51):16297-16301. doi: 10.1002/anie.201710269.
  • Del Signore SJ, Biber SA, Lehmann KS, Heimler SR, Rosenfeld BH, Eskin TL, Sweeney ST, Rodal AA. dOCRL maintains immune cell quiescence by regulating endosomal traffic. PLoS Genet. 2017 Oct 13;13(10):e1007052. doi: 10.1371/journal.pgen.1007052.
  • Del Signore SJ and Rodal AA (2016). The membrane strikes back: phosphoinositide binding regulates Skywalker function. Nat Struct Mol Biol 23(11): 956-957.
  • Deshpande M, Feiger Z, Shilton AK, Luo CC, Silverman E and Rodal AA (2016). Role of BMP receptor traffic in synaptic growth defects in an ALS model. Mol Biol Cell 27(19): 2898-2910.
  • Deshpande M and Rodal AA (2016). Beyond the SNARE: Munc18-1 chaperones alpha-synuclein. J Cell Biol. 2016 Oct 1; 27(19): 2898–2910.
  • Stanishneva-Konovalova TB, Kelley CF, Eskin TL, Messelaar EM, Wasserman SA, Sokolova OS and Rodal AA (2016). Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck. Proc Natl Acad Sci U S A 113(38): E5552-5561.
  • Deshpande M and Rodal AA (2016). The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from DrosophilaTraffic. 2016 Feb;17(2):87-101.
  • Jungmann R, Avendano MS, Dai M, Woehrstein JB, Agasti SS, Feiger Z, Rodal A, Yin P (2016). Quantitative super-resolution imaging with qPAINT. Nature Methods 2016 May;13(5):439-42.
  • Kelley CF, Becalska AN, Berciu C, Nicastro D, Rodal AA (2015). Assembly of actin filaments and microtubules in Nwk F-BAR-induced membrane deformations. Commun Integr Biol. 2015 Apr 29;8(2):e1000703.
  • Kelley CF, Messelaar EM, Eskin TL, Wang S, Song K, Vishnia K, Becalska AN, Shupliakov O, Hagan MF, Danino D, Sokolova OS, Nicastro D, Rodal AA (2015). Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation.  Cell Rep13(11): 2597-2609.
  • Koles K, Messelaar EM, Feiger Z, Yu CJ, Frank CA, Rodal AA (2015). "The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic function." Mol Biol Cell. 2015 Sep 15;26(18):3275-88.
  • Koles K, Yeh AR, Rodal AA (2015). "Tissue-specific tagging of endogenous loci in Drosophila melanogaster." Biol Open 5(1): 83-89.
  • Rodal AA, Del Signore SJ, Martin AC (2015). "Drosophila comes of age as a model system for understanding the function of cytoskeletal proteins in cells, tissues, and organisms." Cytoskeleton (Hoboken). 2015 May;72(5):207-24
  • Frank CA, Wang X, Collins CA, Rodal AA, Yuan Q, Verstreken P, Dickman DK (2013). "New approaches for studying synaptic development, function, and plasticity using Drosophila as a model system." J Neurosci. 2013 Nov 6;33(45):17560-8. .
  • Becalska, AN, Kelley, CF, Berciu, C, Stanishneva-Konovalova, TB, Fu, X, Wang S, Sokolova, OS, Nicastro, D, Rodal, AA (2013). "Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck." Mol Biol Cell. 2013 Aug;24(15):2406-18.
  • Zhao L, Wang, D, Wang, Q, Rodal, AA, Zhang, YQ (2013). "Drosophila cyfip regulates synaptic development and endocytosis by suppressing filamentous actin assembly." PLoS Genet. 2013 Apr;9(4):e1003450.
  • Vizcarra CL, Kreutz B, Rodal AA, Toms AV, Lu J, Zheng W, Quinlan ME, Eck MJ. "Structure and function of the interacting domains of Spire and Fmn-family formins." Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11884-9. Epub 2011 Jul 5.
  • Rodal AA, Blunk AD, Akbergenova Y, Jorquera RA, Buhl LK, Littleton JT. "A presynaptic endosomal membrane trafficking pathway controls synaptic growth signaling." J. Cell Biol. 2011 193(1):201-17.
  • Rodal AA, Motola-Barnes RN, Littleton JT. "Nervous Wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth." J Neurosci. 2008 Aug 13;28(33):8316-25
  • Rodal AA, Littleton JT. "Synaptic endocytosis; illuminating the role of clathrin assembly." Curr Biol. 2008 Mar 25;18(6):R259-61.
  • Rodal AA, Sokolova O, Robins, DB, Daugherty KM, Hippenmeyer S, Riezman H, Grigorieff N, Goode BL. "Conformational changes in the Arp2/3 complex leading to actin nucleation." Nat Struct Mol Biol. 2005 Jan;12(1):26-31.
  • Rodal AA, Kozubowski L, Goode BL, Drubin DG, Hartwig JH. "Actin and septin ultra- structures at the budding yeast cell cortex." Mol Biol Cell. 2005 Jan;16(1):372-84.
  • Rodal AA, Manning AL, Goode BL, Drubin DG. "Negative regulation of yeast WASp by two SH3 domain-containing proteins." Curr Biol. 2003 Jun 17;13(12):1000-8.
  • Sagot, I, Rodal AA, Moseley J, Goode BL, Pellman D. "An actin nucleation mechanism by the formin Bni1 and profilin." Nat Cell Biol.2002 Aug;4(8):626-31.
  • Goode BL, Rodal AA. "Modular complexes that regulate actin assembly in budding yeast." Curr Opin Microbiol. 2001 Dec;4(6):703-12.
  • Goode BL, Rodal AA, Barnes G, Drubin DG. "Activation of the Arp2/3 complex by the actin filament binding protein Abp1p." J Cell Biol. 2001 Apr 30;153(3):627-34.
  • Rodal AA, Tetreault JW, Lappalainen P, Drubin DG, Amberg DC. "Aip1p interacts with cofilin to disassemble actin filaments." J Cell Biol. 1999 Jun 14;145(6):1251-64.