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.
Deshpande M and Rodal AA (2016). "The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila." Traffic. 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 Rep 13(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.
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Last review: June 1, 2016