Expression, characterization, and localization of Rab26, a low molecular weight GTP-binding protein, in the rat parotid gland

Souma, Yoshie; Imai, Akane; Nashida, Tomoko; Shimomura, Hiromi

doi:10.1007/s004180000130

Cited by 39 publications

(24 citation statements)

References 40 publications

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“…Unlike Rab40B that is unique to brain tissue, Rab26 was originally cloned from pancreas (Wagner et al, 1995), a highly active secretory tissue that contains both zymogen and insulin granules, and is localized to secretory granules (Yoshie et al, 2000). Consistent with this observation, expression profiling reveals that Rab26 is strongly up-regulated in pancreatic, liver, and several other secretory tissues ( Figure 1B).…”

Section: The Rabomementioning

confidence: 55%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

114

107

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Rab GTPases and SNARE fusion proteins direct cargo trafficking through the exocytic and endocytic pathways of eukaryotic cells. We have used steady state mRNA expression profiling and computational hierarchical clustering methods to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators in 79 human and 61 mouse nonredundant tissues. We now show that this systems biology approach can be used to define building blocks for membrane trafficking based on Rab-centric protein activity hubs. These Rab-regulated hubs provide a framework for an integrated coding system, the membrome network, which regulates the dynamics of the specialized membrane architecture of differentiated cells. The distribution of Rab-regulated hubs illustrates a number of facets that guides the overall organization of subcellular compartments of cells and tissues through the activity of dynamic protein interaction networks. An interactive website for exploring datasets comprising components of the Rab-regulated hubs that define the membrome of different cell and organ systems in both human and mouse is available at http://www.membrome.org/. INTRODUCTIONUnderstanding the molecular basis for the organization of the exocytic and endocytic membrane trafficking pathways in the eukaryotic cell remains a formidable challenge. The foundation of these pathways is the lipid bilayer that separates different subcellular compartments, their distinguishing features encoded by phospholipid composition, and unique sets of integral and peripheral membrane proteins. By harnessing and regulating the fundamental processes of membrane fission and fusion through the action of protein complexes, the lipid bilayer can be exploited to produce a variety of distinct subcellular compartments with unique chemical environments that play essential roles in cell and organ function. Moreover, it is now evident that these subcellular compartments are dynamic structures in continuous and specific communication through carrier vesicles and tubules that mobilize cargo to specific destinations. They can be disassembled and reassembled in a remarkably facile manner in response to cell signaling pathways, mitosis, or by simple chemical perturbants.Implicit in these dynamic pathways is the need to systematically and reversibly regulate protein interactions. Although traditional phylogenetic analyses provided significant insights into the diversity of components that direct membrane traffic (Pereira-Leal and Seabra, 2000;Chen and Scheller, 2001;Pereira-Leal and Seabra, 2001), our understanding of the basic cellular building blocks that organize this diversity into contiguous pathways is still fragmentary. Reductionist approaches using biochemical and molecular tools also provide important insights into specific steps of a pathway. However, understanding the global interconnectivities of complex biological pathways, such as cargo trafficking, will require new approaches utilizing modern ...

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Section: The Rabomementioning

confidence: 55%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

114

107

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“…However, these earlier results were generated using antibody staining in fixed tissue sections and cell fractionation density gradient enrichment of granules (Nashida et al, 2006;Yoshie et al, 2000). In fact, secretory granules and lysosomes are not easily distinguishable by density gradient properties (Pasquali et al, 1999), and the mature secretory granule markers, syntaxin 6 and c-adaptin, used as markers of secretory granules in previous analyses of RAB26, are also involved in Golgi sorting to lysosomes and late endosomes (Ghosh et al, 2003;Robinson, 1990).…”

Section: Discussionmentioning

confidence: 97%

“…We had previously shown that interfering with RAB26 function inhibited MIST1-mediated granulogenesis (Tian et al, 2010) and hypothesized, based on the initial descriptive publications (Nashida et al, 2006;Wagner et al, 1995;Yoshie et al, 2000), that RAB26 would function somehow to traffic nascent or maturing secretory granules. To study RAB26-secretory-granule interactions, we induced a network of secretory granules by the transfecting secretory cargo RFPtagged Pepsinogen C, in cells stably expressing MIST1, a system we have previously described (Tian et al, 2010).…”

Section: Rab26 Localizes Specifically To Lamp1 Lysosomal Membraneassomentioning

confidence: 99%

RAB26 coordinates lysosome traffic and mitochondrial localization

Jin

Mills

2014

Journal of Cell Science

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As they mature, professional secretory cells like pancreatic acinar and gastric chief cells induce the transcription factor MIST1 (also known as BHLHA15) to substantially scale up production of large secretory granules in a process that involves expansion of apical cytoplasm and redistribution of lysosomes and mitochondria. How a scaling factor like MIST1 rearranges cellular architecture simply by regulating expression levels of its transcriptional targets is unknown. RAB26 is a MIST1 target whose role in MIST1-mediated secretory cell maturation is also unknown. Here, we confirm that RAB26 expression, unlike most Rabs which are ubiquitously expressed, is tissue specific and largely confined to MIST1-expressing secretory tissues. Surprisingly, functional studies showed that RAB26 predominantly associated with LAMP1/cathepsin D lysosomes and not directly with secretory granules. Moreover, increasing RAB26 expression -by inducing differentiation of zymogensecreting cells or by direct transfection -caused lysosomes to coalesce in a central, perinuclear region. Lysosome clustering in turn caused redistribution of mitochondria into distinct subcellular neighborhoods. The data elucidate a novel function for RAB26 and suggest a mechanism for how cells could increase transcription of key effectors to reorganize subcellular compartments during differentiation.

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“…Furthermore, transgenic expression of Rab3d was insufficient to restore the defects caused by the loss of MIST1 function in pancreatic acinar cells (26), indicating that other, as yet unidentified MIST1 targets must also play a role. A RAB paralogous to RAB3D, RAB26, has not been extensively studied, but its expression is restricted to a limited number of highly secretory cells, for which it has been proposed to be involved in regulated vesicular secretion (40,64,67).…”

mentioning

confidence: 99%

RAB26 and RAB3D Are Direct Transcriptional Targets of MIST1 That Regulate Exocrine Granule Maturation

Tian

Jin²,

Bredemeyer³

et al. 2010

Molecular and Cellular Biology

122

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Little is known about how differentiating cells reorganize their cellular structure to perform specialized physiological functions. MIST1, an evolutionarily conserved transcription factor, is required for the formation of large, specialized secretory vesicles in gastric zymogenic (chief) cells (ZCs) as they differentiate from their mucous neck cell progenitors. Here, we show that MIST1 binds to highly conserved CATATG E-boxes to directly activate transcription of 6 genes, including those encoding the small GTPases RAB26 and RAB3D. We next show that RAB26 and RAB3D expression is significantly downregulated in Mist1 ؊/؊ ZCs, suggesting that MIST1 establishes large secretory granules by inducing RAB transcription. To test this hypothesis, we transfected human gastric cancer cell lines stably expressing MIST1 with red fluorescent protein (RFP)-tagged pepsinogen C, a key secretory product of ZCs. Those cells upregulate expression of RAB26 and RAB3D to form large secretory granules, whereas control, non-MIST1-expressing cells do not. Moreover, granule formation in MIST1-expressing cells requires RAB activity because treatment with a RAB prenylation inhibitor and transfection of dominant negative RAB26 abrogate granule formation. Together, our data establish the molecular process by which a transcription factor can directly induce fundamental cellular architecture changes by increasing transcription of specific cellular effectors that act to organize a unique subcellular compartment.

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Expression, characterization, and localization of Rab26, a low molecular weight GTP-binding protein, in the rat parotid gland

Cited by 39 publications

References 40 publications

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

RAB26 coordinates lysosome traffic and mitochondrial localization

RAB26 and RAB3D Are Direct Transcriptional Targets of MIST1 That Regulate Exocrine Granule Maturation

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