My lab is interested in 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 the endosomal system. 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 membrane traffic machinery itself can be regulated to tune signaling up or down. We use a combination of biochemistry, genetics, and live imaging in the fruit fly nervous system to unravel the molecular mechanisms by which the traffic of signaling receptors that control the architecture of synapses is regulated by conserved endosomal trafficking machinery.
Neurons are exquisitely specialized for this type of membrane traffic because they must efficiently package and repackage neurotransmitters, the chemical messengers of neuron-to-neuron communication, into synaptic vesicles in response to electrical impulses. The set of cellular machinery that controls the formation, reformation, and movement of vesicles containing neurotransmitters overlaps extensively with the machinery that controls the internalization of growth and survival signaling cargo. We are investigating how neuron-specific mechanisms of controlling membrane traffic of synaptic vesicles in response to electrical activity can also apply to signaling receptor traffic. We are particularly focused on a network of proteins that bind to the endosomal membrane and drive the formation and scission of cargo-containing tubules. These proteins include Nwk (Nervous Wreck) a neuronal member of the F-BAR/SH3 protein family that ties membrane deformation to force-generating actin filament polymerization, and dynamin, the GTPase that drives vesicle scission. These trafficking events are implicated in diseases ranging from cancer to mental retardation, neurodegenerative disease and addiction, underlining the health importance of understanding how signal transduction is modulated by intracellular membrane traffic.
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. [abstract]
Rodal AA, Blunk AD, Akbergenova Y, Jorquera RA, Buhl LK, Littleton JT. A presynaptic endosomal trafficking pathway controls synaptic growth signaling. J Cell Biol. 2011 Apr 4;193(1):201-17. [abstract]
Rodal AA, Motola-Barnes RN, Littleton JT. Nervous Wreck and Cdc42 cooperate to regulate endocytic actin assembly during synaptic growth. J. Neurosci. 2008 28(33):8316-25.
Rodal AA, Littleton JT. Synaptic endocytosis; illuminating the role of clathrin assembly. Curr Biol. 2008 18(6): R259-261.
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. Nature 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 15, 2012