![]() As Christian De Duve suggested ( 151), this might have happened as a consequence of the selective pressure provided by the transition from “the primordial soup to oceans,” i.e., from environments in which nutrients were present in a concentrated form to diluted environments. As prokaryotes evolved to eukaryotes, more complex “entry portals” began to appear. Early prokaryotic life forms used relative simple devices, such as pumps or channels, to transport essential molecules, such sugars, amino acids, and ions, through the PM. For the sake of clarity, however, we would be wise to take things from the beginning. This is because the past is paradoxically the best bridge between the present and the future, or, in other words, because the evolutionary perspective, though speculative, can help us to rationalize a number of heterogeneous observations and can indicate which experimental strategies might serve to achieve a coherent biological picture of endocytosis. The attentive reader will notice that this review ends where it should have started, i.e., with a discussion of the evolution of endocytosis and of the endomembrane system. The declared intent of this review is to illustrate how we have moved, in the course of the past 15 years or so, from one outlook to the other. ![]() ![]() Its evolution constitutes, arguably, the major driving force in the evolution of prokaryotic to eukaryotic organisms.” A shorter version might read as follows: “Endocytosis is the logistics of the cell,” where logistics (again as defined by Wiki) “involves the integration of information, transportation, inventory, warehousing, material handling and packaging, and security,” or in brief “having the right thing, in the right place, at the right time.” This latter definition of endocytosis underscores a shift from a limited perspective (what we might call a “traditional view”) to a much wider one, in which endocytosis is the cornerstone of the eukaryotic cell project. As such, it governs almost all aspects of the relationships of the cell with the extracellular environment and of intracellular communication. Based on present knowledge, a more precise definition of endocytosis should read: “a vast program, deeply ingrained in the cellular master plan and inextricably intertwined with signaling, which constitutes the major communications infrastructure of the cell. However, this is only a fragment of the whole picture. Indeed, endocytosis most likely evolved for this purpose. I. Introduction: The Vantage Point of Endocytosis on Signaling (and Vice Versa)Ī search for the term endocytosis in any major cell biology textbook, in the Encyclopedia Britannica, or even in Wikipedia will result in a definition corresponding to a more or less sophisticated version of the following (taken from Wiki): “Endocytosis is the process by which cells absorb molecules … that cannot pass through the plasma membrane.” This is indeed true endocytosis serves to bring nutrients and/or other types of molecules into the cell and, at the same time, to regulate the composition of the plasma membrane (PM). By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan. A possible framework, to rationalize all this new knowledge, requires us to “upgrade” our vision of endocytosis. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Our understanding of endocytosis has evolved remarkably in little more than a decade.
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