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The inner workings of intracellular heterotypic and homotypic membrane fusion mechanisms

Abstract

Intracellular trafficking is a field that has been intensively studied for years and yet there remains much to be learned. Part of the reason that there is so much obscurity remaining in this field is due to all the pathways and the stages that define cellular trafficking. One of the major steps in cellular trafficking is fusion. Fusion is defined as the terminal step that occurs when a cargo-laden vesicle arrives at the proper destination. There are two types of fusion within a cell: homotypic and heterotypic fusion. Homotypic fusion occurs when the two membranes merging together are of the same type such as vacuole to vacuole fusion. Heterotypic fusion occurs when the two membranes at play are of different types such as when an endosomal membrane fuses with a Golgi membrane. In this review, we will focus on all the protein components – Rabs, Golgins, Multisubunit tethers, GTPases, protein phosphatases and SNAREs – that have been known to function in both of these types of fusion. We hope to develop a model of how all of these constituents function together to achieve membrane fusion. Membrane fusion is a biological process absolutely necessary for proper intracellular trafficking. Due to the degree of importance multiple proteins are required for it to be properly carried through. Whether we are talking about heterotypic or homotypic fusion, any defects in the fusion machinery can result in disease states such as Parkinson’s and Alzheimer’s disease. Although much research has significantly expanded our knowledge of fusion, there is still much more to be learned.

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Abbreviations

COG:

Conserved oligomeric Golgi complex. A multi tethering complex composed of eight subunits known to be localized to the Golgi membrane

GARP:

Golgi-associated retrograde protein. A multi tethering complex composed of four subunits known to be localized to the Golgi membrane

Golgin:

Coiled-coil protein known to localized primarily to the Golgi membrane

MTC:

Multi-tethering complex. Name given to tethers known to be made up by many protein subunits

Rab:

Small GTPase that is part of the Ras superfamily

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

Vps1:

Vacuolar protein sorting-associated protein 1. Yeast homologue to dynamin. GTPase protein

LMA1:

Vacuolar binding protein that aids in Vam3 retention prior to fusion

Sec17:

Alpha-soluble NSF attachment protein. Protein that binds to cis-SNAREs

Sec18:

ATPase involved in SNARE disassembly along with Sec17

HOPS:

Multi tethering complex that functions in vacuolar fusion

YcK3p:

Kinase that phosphorylates Vps41 of the HOPS complex

Mon1–Ccz1:

Guanine nucleotide exchange factor of Ypt7

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Acknowledgements

The authors acknowledge Missouri State University for providing the resources necessary to conduct literature research to write this review.

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Correspondence to Kyoungtae Kim.

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Communicated by Amitabha Chattopadhyay.

Corresponding editor: Amitabha Chattopadhyay

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Delgado Cruz, M., Kim, K. The inner workings of intracellular heterotypic and homotypic membrane fusion mechanisms. J Biosci 44, 91 (2019). https://doi.org/10.1007/s12038-019-9913-3

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Keywords

  • Golgi
  • Rabs
  • SNAREs
  • tethers
  • vacuole