The Fromme Lab

Recent Fromme Lab News:

Research Focus:  The Golgi complex is the “Grand Central Station” within our cells, serving as the primary sorting organelle at the nexus of the secretory and endocytic trafficking pathways. For example, virtually all proteins that eukaryotic cells display on their surface at the plasma membrane are first synthesized at the endoplasmic reticulum and then trafficked to the Golgi complex.  Once at the Golgi, proteins find themselves at a crossroads: they may be trafficked to the plasma membrane, to endocytic organelles, to lysosomal organelles, back to the endoplasmic reticulum, or they may remain within the Golgi complex. We view the Golgi as an excellent model for investigating how decisions are made at the level of an organelle: How does the Golgi maintain homeostasis in the face of constant flux? How does the Golgi respond to changes in cargo load? Does the Golgi communicate with other organelles?

The regulators for all incoming and outgoing Golgi traffic are GTPases of the Rab and Arf families. Arf and Rab proteins are activated by GEFs (guanine nucleotide exchange factors), which are master regulators of trafficking pathways. Despite knowing the identity of many of these regulators, the molecular and atomic basis for their regulation remains poorly defined.

Our lab discovered that Arf activation is regulated at the Golgi through GEF autoinhibition, positive feedback, and GTPase crosstalk mechanisms. Our findings lead to a model for regulation of the Golgi in which multiple GTPases pathways, previously considered to act in isolation, are intimately connected. This model is powerful because it enables us to answer questions within a GEF-centric framework. By investigating how the GEFs are regulated using biochemical, structural, and cell biological approaches, we aim to uncover the molecular logic governing regulation of the Golgi at a mechanistic level.

Golgi trafficking is controlled by a discrete set of GTPases

August 2015 Golgi_intro_GTPases_A

Chris Fromme, Ph.D.

Chris Fromme is an Associate Professor in the Weill Institute for Cell and Molecular Biology and the Department of Molecular Biology and Genetics. After graduating from Cornell with a B.A. in Biology in 1999, Chris did his graduate studies at Harvard University, receiving a Ph.D. in Biochemistry in 2004. He then did postdoctoral work as a Miller Institute Fellow at UC Berkeley, where he began his work on protein trafficking and membrane transport. He joined the Cornell faculty in 2008.

Chris Fromme, Ph.D
Weill Institute for Cell and Molecular Biology
Department of Molecular Biology and Genetics
Cornell University
457 Weill Hall
Ithaca, NY 14853-7202

jcf14@cornell.edu

(607)255-1016 (Office)
(607)255-7834 (Lab)

Selected Publications

Richardson, B.C., Halaby, S.L., Gustafson, M.A., and Fromme, J.C. The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase. eLife.. 10.7554/eLife.12411.

Paczkowski, J.E., Richardson, B.C., and Fromme, J.C. Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis. Trends Cell Biol.. 10.1016/j.tcb.2015.02.005.

McDonold, C.M., and Fromme, J.C. Four GTPases differentially regulate the Sec7 Arf-GEF to direct traffic at the trans-Golgi network.   Dev. Cell. 2014 Sept 29; 30(6): 759-767.

Paczkowski, J.E., and Fromme, J.C. Structural basis for membrane binding and remodeling by the exomer secretory vesicle cargo adaptor.   Dev. Cell. 2014 Sept 8; 30(5): 610-624.

Weiskoff, A.M., and Fromme, J.C. Distinct N-terminal regions of the exomer secretory vesicle cargo Chs3 regulate its trafficking itinerary.   Front. Cell Dev. Biol.. 2014 Sept 3; 2: 10.3389/fcell.2014.00047.

Richardson BC, Fromme JC. The exomer cargo adaptor features a flexible hinge domain.  Structure. 2013 Mar 5; 21(3):486-92. doi: 10.1016/j.str.2013.01.003. Epub 2013 Feb 7.

Paczkowski JE, Richardson BC, Strassner AM, Fromme JC. The exomer cargo adaptor structure reveals a novel GTPase-binding domain.  EMBO J. 2012 Nov 5; 31(21):4191-203. doi: 10.1038/emboj.2012.268. Epub 2012 Sep 21.

Richardson BC, McDonold CM, Fromme JC. The Sec7 Arf-GEF is recruited to the trans-Golgi network by positive feedback. Dev Cell. 2012 Apr 17; 22(4):799-810. doi: 10.1016/j.devcel.2012.02.006.

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