Models of Intracellular Transport: Contradictions and Current Understanding.

Intracellular transport is one of the most complex and debated topics in cell biology. Numerous models and their combinations have been proposed to explain experimental data on this process. This article describes our current understanding of the secretory pathway by analyzing different transport models. To identify the most realistic model, we identified observations that cannot be fully explained by the vesicular, diffusion, or cisterna maturation-progression models. The kiss-and-run model appears as the most powerful. From this perspective, vesicles at the ER exit sites are considered to be COPI-dependent. In cells with the central Golgi, the movement of carriers between the Golgi and peripheral structures occurs along microtubules via a bolus-like mechanism. In cells lacking microtubules, free ER-to-Golgi and Golgi-to-plasmalemma (or Golgi-to-endosome) carriers are extremely rare. Intra-Golgi transport relies heavily on temporary connections between cisternae, which subsequently break down. Cisternal perforations play a crucial role in this process. Cargo moves directionally through the Golgi stack, reaching the last two medial-cisternae and/or the trans-most cisterna, which function as the Golgi exit site. At this point, the dynamics of transport shifts from linear cargo movement to an exponential decay pattern. Post-Golgi carriers have to replace their own SNAREs with SNAREs that are able to facilitate their fusion with the plasmalemma.