TY - JOUR
T1 - The Diffusion Model of Intra-Golgi Transport Has Limited Power
AU - Beznoussenko, Galina V.
AU - Bejan, Andrei Iu
AU - Parashuraman, Seetharaman
AU - Luini, Alberto
AU - Kweon, Hee Seok
AU - Mironov, Alexander A.
N1 - Funding Information:
We thank all of scientists who sent us their reagents; Daniele Di Giandomenico and A. Fusella for help in EM preparations; Micaela Quarto for her help in the manuscript corrections, and M. Rekhter for discussion, critical suggestions, and the editing of the manuscript. We acknowledge Italian FIRC’s support of laboratory (to A.A.M.), INTAS (Project 99-4-1732; (to A.A.M.), Telethon (E.1105), the Italian National Research Council (Convenzione CNR–Consorzio Mario Negri Sud) to A.A.M.; Consorzio Mario Negri Sud for the laboratory support (to G.V.B.). We acknowledge the Centre European of Nano-medicine (Italy) for the chance to use the Tecnai 20 electron microscope.
Funding Information:
This research was funded by Mario Negri institute.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/1/10
Y1 - 2023/1/10
N2 - The Golgi complex (GC) is the main station along the cell biosecretory pathway. Until now, mechanisms of intra-Golgi transport (IGT) have remained unclear. Herein, we confirm that the goodness-of-fit of the regression lines describing the exit of a cargo from the Golgi zone (GZ) corresponds to an exponential decay. When the GC was empty before the re-initiation of the intra-Golgi transport, this parameter of the curves describing the kinetics of different cargoes (which are deleted in Golgi vesicles) with different diffusional mobilities within the GZ as well as their exit from the GZ was maximal for the piecewise nonlinear regression, wherein the first segment was horizontal, while the second segment was similar to the exponential decay. The kinetic curve describing cargo exit from the GC per se resembled a linear decay. The Monte-Carlo simulation revealed that such curves reflect the role of microtubule growth in cells with a central GC or the random hovering of ministacks in cells lacking a microtubule. The synchronization of cargo exit from the GC already filled with a cargo using the wave synchronization protocol did not reveal the equilibration of cargo within a Golgi stack, which would be expected from the diffusion model (DM) of IGT. Moreover, not all cisternae are connected to each other in mini-stacks that are transporting membrane proteins. Finally, the kinetics of post-Golgi carriers and the important role of SNAREs for IGT at different level of IGT also argue against the DM of IGT.
AB - The Golgi complex (GC) is the main station along the cell biosecretory pathway. Until now, mechanisms of intra-Golgi transport (IGT) have remained unclear. Herein, we confirm that the goodness-of-fit of the regression lines describing the exit of a cargo from the Golgi zone (GZ) corresponds to an exponential decay. When the GC was empty before the re-initiation of the intra-Golgi transport, this parameter of the curves describing the kinetics of different cargoes (which are deleted in Golgi vesicles) with different diffusional mobilities within the GZ as well as their exit from the GZ was maximal for the piecewise nonlinear regression, wherein the first segment was horizontal, while the second segment was similar to the exponential decay. The kinetic curve describing cargo exit from the GC per se resembled a linear decay. The Monte-Carlo simulation revealed that such curves reflect the role of microtubule growth in cells with a central GC or the random hovering of ministacks in cells lacking a microtubule. The synchronization of cargo exit from the GC already filled with a cargo using the wave synchronization protocol did not reveal the equilibration of cargo within a Golgi stack, which would be expected from the diffusion model (DM) of IGT. Moreover, not all cisternae are connected to each other in mini-stacks that are transporting membrane proteins. Finally, the kinetics of post-Golgi carriers and the important role of SNAREs for IGT at different level of IGT also argue against the DM of IGT.
KW - COPI vesicle
KW - diffusion model
KW - Golgi apparatus
KW - Golgi complex
KW - intracellular transport
KW - kiss-and-run
UR - http://www.scopus.com/inward/record.url?scp=85146746423&partnerID=8YFLogxK
U2 - 10.3390/ijms24021375
DO - 10.3390/ijms24021375
M3 - Article
C2 - 36674888
AN - SCOPUS:85146746423
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 2
M1 - 1375
ER -