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==History== The discovery of major principles of cell secretion started between the 1940’s and 50’s, which has helped to understand cellular transport mechanisms. The discovery of lysosome exocytosis in the 1950s was made possible by early research on the endoplasmic reticulum by Keith Porter, Albert Claude, and George Palade, which resulted from the development of electron microscopy.<ref name="Verhage-2008" /> This has given a greater understanding of the membrane trafficking and vesicle transport, which in turn provides information about cell communication and its environment. Some important milestones in exocytosis research: * '''1950s-1960s''': The basic elements and functions of the term exocytosis was discovered, and the word exocytosis was used to describe vesicle-mediated secretion processes, with emphasis on the role within neurotransmitter release and hormone secretion.<ref name="Verhage-2008" /> * '''1970s-1980s''': The SNARE proteins were identified after a decade of biochemical research, through an in-vitro trafficking assay developed in the 80’s by Rothman et. Al. The synaptic SNAREs identified were discovered in either synaptic vesicles or presynaptic membrane.<ref name="Ungar-2003">{{cite journal |last1=Ungar |first1=Daniel |last2=Hughson |first2=Frederick M. |title=SNARE Protein Structure and Function |journal=Annual Review of Cell and Developmental Biology |date=November 2003 |volume=19 |issue=1 |pages=493–517 |doi=10.1146/annurev.cellbio.19.110701.155609 |pmid=14570579 }}</ref> This led to research that uncovered their critical role in vesicle docking and fusion with the plasma membrane <ref name="Jahn-2006">{{cite journal |last1=Jahn |first1=Reinhard |last2=Scheller |first2=Richard H. |title=SNAREs — engines for membrane fusion |journal=Nature Reviews Molecular Cell Biology |date=September 2006 |volume=7 |issue=9 |pages=631–643 |doi=10.1038/nrm2002 |pmid=16912714 |hdl=11858/00-001M-0000-0012-E3F4-9 |hdl-access=free }}</ref> and led to an understanding of the processes that trigger exocytosis, such as increased calcium concentration.<ref name="Stojilkovic Ca2+-regulated exocytosis">{{cite journal |last1=Stojilkovic |first1=Stanko S. |title=Ca2+-regulated exocytosis and SNARE function |journal=Trends in Endocrinology & Metabolism |date=April 2005 |volume=16 |issue=3 |pages=81–83 |doi=10.1016/j.tem.2005.02.002 |pmid=15808803 }}</ref> * '''1993''': James E. Rothman, Randy W. Schekman, and Thomas C.Südhof made groundbreaking contributions to understanding vesicle transport, earning the Nobel Prize in Physiology or Medicine in 2013. Their research elucidated the mechanisms of vesicle trafficking, fusion, and cargo release.<ref>{{cite journal |last1=Südhof |first1=Thomas C. |title=Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle |journal=Neuron |date=October 2013 |volume=80 |issue=3 |pages=675–690 |doi=10.1016/j.neuron.2013.10.022 |pmc=3866025 |pmid=24183019 }}</ref> * '''2000s-Present''': The development of new and advanced imaging techniques, such as [[fluorescence imaging]] allowed for real-time monitoring of exocytosis.<ref name="Tran-2017">{{Cite journal |last1=Tran |first1=Duy T. |last2=Ten Hagen |first2=Kelly G. |date=2017-04-15 |title=Real-time insights into regulated exocytosis |journal=Journal of Cell Science |volume=130 |issue=8 |pages=1355–1363 |doi=10.1242/jcs.193425 |pmid=28302911 |pmc=5399783 }}</ref> This provides new insights into molecular mechanisms, such as multiple pathways, kiss-and-run and the process of exocytosis to a more detailed level.<ref name="Gruschus-2021">{{cite book |doi=10.1016/B978-0-323-85707-9.00011-3 |chapter=Shapeshifter – the molecular structure and normal biological role of synuclein in neurons |title=Synuclein and the Coelacanth |date=2021 |last1=Gruschus |first1=James M. |pages=69–87 |isbn=978-0-323-85707-9 }}</ref>
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