Abstract
Transport of proteins and lipids from one membrane compartment to another is via intracellular vesicles. We investigated the function of tumor protein D54 (TPD54/TPD52L2) and found that TPD54 was involved in multiple membrane trafficking pathways: anterograde traffic, recycling, and Golgi integrity. To understand how TPD54 controls these diverse functions, we used an inducible method to reroute TPD54 to mitochondria. Surprisingly, this manipulation resulted in the capture of many small vesicles (30 nm diameter) at the mitochondrial surface. Super-resolution imaging confirmed the presence of similarly sized TPD54-positive structures under normal conditions. It appears that TPD54 defines a new class of transport vesicle, which we term intracellular nanovesicles (INVs). INVs meet three criteria for functionality. They contain specific cargo, they have certain R-SNAREs for fusion, and they are endowed with a variety of Rab GTPases (16 out of 43 tested). The molecular heterogeneity of INVs and the diverse functions of TPD54 suggest that INVs have various membrane origins and a number of destinations. We propose that INVs are a generic class of transport vesicle that transfer cargo between these varied locations.
Highlights
Eukaryotic cells are by definition compartmentalized: they series of cancers (Cao et al, 2006; Byrne et al, 1995, 1998; contain organelles and membrane-bound domains that have Nourse et al, 1998)
TPD52 is involved in secoated vesicles (50–100 nm diameter) formed at the plasma cretion in pancreatic acinar cells (Thomas et al, 2004, 2010; membrane (PM) or TGN, COPII-coated vesicles (60–70 nm) orig- Messenger et al, 2013) and potentially at synapses (Biesemann inating at the ER, and intra-Golgi transport vesicles (70–90 nm; et al, 2014)
TPD54 is a membrane trafficking protein To investigate the subcellular localization of TPD54, we generated a cell line where TPD54 was tagged at its endogenous locus with monomeric GFP (Fig. 1 and Fig. S1)
Summary
Eukaryotic cells are by definition compartmentalized: they series of cancers (Cao et al, 2006; Byrne et al, 1995, 1998; contain organelles and membrane-bound domains that have Nourse et al, 1998). Overexpression of TPD52 correlates with distinct identities. Vesicle transport between these locations is poor prognosis in breast cancer patients, and in cell models, tightly regulated to maintain these identities, yet allows ex- TPD52 overexpression promotes proliferation and invasion change of specific materials. Whether cell TPD52, such as the endocytic protein Rab5c (Shahheydari et al, biologists have a complete inventory of vesicular carriers is an 2014), and the transcytotic protein MAL2 (Wilson et al, 2001)
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