Positive feedback between golgi membranes, microtubules and ER-exit sites directs golgi de novo biogenesis

Abstract

The Golgi complex is the central organelle of the secretory pathway. It undergoes dynamic changes during the cell cycle, but how it acquires and maintains its complex structure is unclear. To address this question, we have used laser nanosurgery to deplete BSC1 cells of the Golgi complex and have monitored its biogenesis by quantitative time-lapse microscopy and correlative electron microscopy. After Golgi depletion, endoplasmic reticulum (ER) export is inhibited and the number of ER exit sites (ERES) is reduced and does not increase for several hours. Occasional fusion of small post-ER carriers to form the first larger structures triggers a rapid and drastic growth of Golgi precursors, due to the capacity of these structures to attract more carriers by microtubule nucleation and to stimulate ERES biogenesis. Increasing the chances of post-ER carrier fusion close to ERES by depolymerizing microtubules results in the acceleration of Golgi and ERES biogenesis. Taken together, on the basis of our results, we propose a self-organizing principle of the early secretory pathway that integrates Golgi biogenesis, ERES biogenesis and the organization of the microtubule network by positive-feedback loops.

Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei

“…The Golgi is clearly a very dynamic structure, and its structure and function has been argued to rely on the integrity of export from the ER . Similarly, when mammalian cells were depleted of Golgi bodies using laser nanosurgery, there was a reduction in the number of ERES and reduced ER export . This argues for an interplay between the two structures.…”

COPII gets in shape: Lessons derived from morphological aspects of early secretion

“…A functional link between donor‐acceptor membrane interactions and coat assembly is observed on a more global level, when the assembly of COPII‐coated ERES is measured following the ablation of acceptor Golgi membranes. Golgi ablation dramatically reduced the number of COPII‐coated ERES and this effect is reversed by maintaining proximity between ERES and acceptor Golgi membranes …”

GM130 and p115 play a key role in the organisation of the early secretory pathway during skeletal muscle differentiation

“…The data described above, together with previous work showing that GC and ERES organisation persist despite the lack of normal microtubule tracks in differentiating SKM cells (Zaal et al, 2011), and the growing evidence of a reciprocal regulation of GC and ERES (Glick, 2014;Ronchi et al, 2014), introduces the hypothesis that the GC also has a leading role in ERES positioning in differentiating C 2 C 12 cells. To test this hypothesis, we perturbed the GC organisation by treating cells with the fungal metabolite brefeldin A (BFA) (Lippincott-Schwartz et al, 1989) and followed ERES behaviour in differentiating SKM cells.…”

“…The growing opinion that GC and ERES are capable of a reciprocal fine regulation (Glick, 2014;Ronchi et al, 2014), and the increasing evidence of a strong correlation between human diseases and the shape and function of the GC (Bexiga and Simpson, 2013;Percival and Froehner, 2007) oriented our work at further understanding the mechanisms responsible of the close correlation between GC and ERES and its importance for SKM differentiation and fusion.…”