Abstract
The study of membrane traffic is now a well-established area of research, and one that has resulted in several Nobel prizes including ones awarded to Albert Claude, George Palade, and Christian DeDuve in 1974, Michael Brown and Joseph Goldstein in 1985, Gunter Blobel in 1999, and most recently James Rothman, Randy Schekman, and Thomas Sudhof in 2013. As a result of their studies and other research, we now have fundamental insights into the organization and routes of transport between the cells' membranous organelles. Moreover, we have defined the basic “cellular machinery” that governs protein and lipid synthesis, that ensures selective recognition of proteins and lipids, and that promotes vesicle fission, transport, and fusion. In addition, we have a large number of insights into the regulatory molecules that control these processes including the Rab GTPases and their effectors. While the challenges for the future are many, this essay is focused on areas of investigation that we see as moving forward at a rapid pace, which speak to how membrane traffic contributes to overall cell and tissue function, and which are likely to provide important avenues of funding for both established and new investigators. These challenges include how membrane traffic is regulated in response to metabolic needs, how molecules are transferred between organelles, how membrane traffic is regulated and functions during processes such as development, and how membrane traffic is used by highly differentiated cells to perform specialized cell functions.
Highlights
The study of membrane traffic is a well-established area of research, and one that has resulted in several Nobel prizes including ones awarded to Albert Claude, George Palade, and Christian DeDuve in 1974, Michael Brown and Joseph Goldstein in 1985, Gunter Blobel in 1999, and most recently James Rothman, Randy Schekman, and Thomas Südhof in 2013
These challenges include how membrane traffic is regulated in response to metabolic needs, how molecules are transferred between organelles, how membrane traffic is regulated and functions during processes such as development, and how membrane traffic is used by highly differentiated cells to perform specialized cell functions
In the case of insulin, the PI3K/Akt pathway may play a critical role by regulating the traffic of the SREBP cleavage-activating protein” (SCAP)-sterol regulatory element binding proteins” (SREBPs) complex from the endoplasmic reticulum (ER) to Golgi by phosphorylating SREBP1c and modulating its affinity for Sar1p and Sec23/24 at the expense of interactions with insulin-induced gene” (Insig) (Yellaturu et al, 2009a,b)
Summary
SPECIALTY GRAND CHALLENGE ARTICLE published: 17 September 2014 doi: 10.3389/fcell.2014.00052 Edited and reviewed by: Steve Caplan, University of Nebraska Medical Center, USA Rytis Prekeris, University of Colorado Anschutz Medical Campus, USA Keywords: membrane contact sites, mTORC1 signaling, SREBPs, lipid droplets, store-operated Ca2+ entry, Notch signaling, umbrella cell, t-cell synapse
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