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Developmental Biology - Trans Golgi Network

How A Cell Sorts & Distributes Molecules

Re-evaluating how a molecular "sorting station" maintains our cellular machinery....


When a molecule bumps up to a cell wall it is immediately surrounded by a portion of the cell wall's outer membrane, encasing it in a membranous sac. This is "invagination."

Sorting

Substances from early endosomes can be recycled back through the cell membrane to exit the cell, or sent on to a lysosome full of enzymes that further breakdown or dissolve the molecule for recycling.
Endosome can be either nutrients, molecular signals needing to be further processed onto other cells, or perhaps dangerous pathogenic viruses that cause disease. So, it is extremely important to completely understand everything about how endosome sacs form and are dispersed.

It's generally accepted that endosomes sacs shed off the cell membrane constantly. But a recent study published in Communications Biology, by a group from the Tokyo University of Science, observed that the trans-Golgi network, another cell organelle made up of long sac like structures, is even more important to the formation and maintenance of endosomes.
"We used our research to show that endocytic vesicle internalization is not essential, but that vesicle transport from the trans-Golgi network is crucial."

Jiro Toshima PhD, Professor, Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan.

The scientists base their claim on observations of a series of experiments isolating steps in the endocytosis process. They identified that early endosome existence, thought to be maintained by the continual fusion of transport vesicles from the plasma membrane and the trans-Golgi network (TGN) - is instead dispensable. But, the post-Golgi vesicle transport is crucial in the formation of endosomes and the following endolysosomal traffic regulated by the yeast Rab5 Vps21p.

Further experiments revealed that smaller amounts of Rab5 localized on endosomes, hamper endosome formation.

Trans-Golgi Network

Toshima's group identified proteins, either resident in the Golgi or recruited to it, are transported to endosomes where they activate Rab5 — and spark formation of more endosomes. Deleting or deactivating those genes negatively affects endosome formation.
Considering all of these results, it appears endocytosis is not necessary for endosome formation and maintenance, but vesicle transport from the Golgi is critical.

"Our results provide a different view of endosome formation and identify the trans-Golgi network (TGN) as a critical location for optimal maintenance and functioning of endosomes," explains Toshima.

The study reveals only a fraction of how cellular mechanisms interconnect within a cell, and much remains to be discovered. Even so, this information of how one core pathway works within a cell enhances the comprehension of molecular disease.

Abstract
Early endosomes, also called sorting endosomes, are known to mature into late endosomes via the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence is thought to be maintained by the continual fusion of transport vesicles from the plasma membrane and the trans-Golgi network (TGN). Here we show instead that endocytosis is dispensable and post-Golgi vesicle transport is crucial for the formation of endosomes and the subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all three proteins required for endosomal nucleotide exchange on Vps21p are first recruited to the TGN before transport to the endosome, namely the GEF Vps9p and the epsin-related adaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, with Vps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These results provide a different view of endosome formation and identify the TGN as a critical location for regulating progress through the endolysosomal trafficking pathway.

Authors
Makoto Nagano, Junko Y. Toshima, Daria Elisabeth Siekhaus and Jiro Toshima.


Acknowledgments
About the Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of "Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.
Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Jiro Toshima from the Tokyo
University of Science
Dr Jiro Toshima is at present a Professor with the Department of Biological Science and Technology at the Tokyo University of Science, Japan. Having begun research in cell biology and related fields in 1999, he has co-authored over 41 publications, and is the lead author of the present paper. From September 2017, he has served as a Councillor in the Japanese Biochemical Society.


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Formation & maintenance of endosomes is governed by the trans-Golgi network (TGN).
CREDIT Tokyo University of Science.


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