The Regulation of Rab GTPases by Phosphorylation

Xu, Lejia; Nagai, Yuki; Kajihara, Yotaro; Ito, Genta; Tomita, Taisuke

doi:10.3390/biom11091340

Cited by 19 publications

(9 citation statements)

References 91 publications

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“…Rab10 is involved in a myriad of functions in the polarized transport of proteins from the Golgi to the plasma membrane [ 37 ], and in exocytosis [ 38 ] and endosomal sorting [ 39 ] in polarized cells. Accumulated findings have suggested that the dynamic control of the Rab function is more regulated by phosphorylation [ 40 , 41 ]. We have found that non-phosphorylated Rab8b or Rab10 resulted in cell bulging, probably due to protein retention in the cells with disorder of polarized transport ( Figure 4 C).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian

Wang

Ouyang

Tan

et al. 2023

Cells

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The dual-specificity tyrosine phosphorylation-regulated kinase (DYRK1) phosphorylates diverse substrates involved in various cellular processes. Here, we found that blocking the kinase activity of DYRK1 inhibited notochord development and lumenogenesis in ascidian Ciona savignyi. By performing phosphoproteomics in conjunction with notochord-specific proteomics, we identified 1065 notochord-specific phosphoproteins that were present during lumen inflation, of which 428 differentially phosphorylated proteins (DPPs) were identified after inhibition of DYRK1 kinase activity. These DPPs were significantly enriched in metal ion transmembrane transporter activity, protein transport and localization, and tight junction. We next analyzed the downregulated phosphoproteins and focused on those belonging to the solute carrier (SLC), Ras-related protein (RAB), and tight junction protein (TJP) families. In vivo phospho-deficient study showed that alanine mutations on the phosphosites of these proteins resulted in defects of lumenogenesis during Ciona notochord development, demonstrating the crucial roles of phosphorylation of transmembrane transport-, vesicle trafficking-, and tight junction-related proteins in lumen formation. Overall, our study provides a valuable data resource for investigating notochord lumenogenesis and uncovers the molecular mechanisms of DYRK1-mediated notochord development and lumen inflation.

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Section: Discussionmentioning

confidence: 99%

Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian

Wang

Ouyang

Tan

et al. 2023

Cells

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“…The LRRK2-dependent phosphorylation of Rab10 in the highly conserved switch II region has been proposed to affect its GTP/GDP cycle as well as its ability to bind effectors 44,45 . Moreover, this phosphorylation site has been shown to regulate the interaction of Rab10 with JIP3 and JIP4 46 , which are adaptors for the plus-end-directed microtubule-dependent motor kinesin-1 47,48 .…”

Section: Discussionmentioning

confidence: 99%

Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport

Lazo

Schiavo²

2021

Preprint

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The extreme, complex morphology of neurons provides an unrivalled model to study the coordination between local signalling and long-range cell responses. A cogent example is provided by the binding of brain- derived neurotrophic factor (BDNF) to its receptor TrkB, which triggers signalling cascades at axon terminals that result in responses at the level of the cell body, including modulation of gene expression. Retrograde propagation of these critical signals relies on the sorting of activated TrkB receptors to retrograde axonal transport organelles termed signalling endosomes. In this work, we show that the small GTPase Rab10 is critical for the sorting of activated TrkB receptors to axonal retrograde carriers and the propagation of neurotrophin signalling from the axon terminal to the soma. Moreover, our data indicate that Rab10 defines a novel class of axonal organelles that are mobilised towards the axon terminal upon BDNF stimulation, thus enabling the axon to dynamically adjust the retrograde signalling flow to changes in BDNF availability at the synapse.

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“…Rabs, small GTPases that play an essential role in intracellular vesicular transport, serve as key switches that regulate membrane transport within eukaryotic cells. Rab proteins interact with their binding domain (RBD) to recruit Rab effectors into subcellular compartments via their binding domain, regulating vesicle formation, transport, and fusion processes [114][115][116]. Leucine-rich repeat kinase 2 (LRRK2) can directly phosphorylate Rabs; when overexpressed, 14 Rabs become substrates of endogenous LRRK2.…”

Section: Golgi Apparatus-parkinsonmentioning

confidence: 99%

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Mohan,

Calenic,

Ghiurau

et al. 2023

Cells

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This comprehensive review article dives deep into the Golgi apparatus, an essential organelle in cellular biology. Beginning with its discovery during the 19th century until today’s recognition as an important contributor to cell function. We explore its unique organization and structure as well as its roles in protein processing, sorting, and lipid biogenesis, which play key roles in maintaining homeostasis in cellular biology. This article further explores Golgi biogenesis, exploring its intricate processes and dynamics that contribute to its formation and function. One key focus is its role in neurodegenerative diseases like Parkinson’s, where changes to the structure or function of the Golgi apparatus may lead to their onset or progression, emphasizing its key importance in neuronal health. At the same time, we examine the intriguing relationship between Golgi stress and endoplasmic reticulum (ER) stress, providing insights into their interplay as two major cellular stress response pathways. Such interdependence provides a greater understanding of cellular reactions to protein misfolding and accumulation, hallmark features of many neurodegenerative diseases. In summary, this review offers an exhaustive examination of the Golgi apparatus, from its historical background to its role in health and disease. Additionally, this examination emphasizes the necessity of further research in this field in order to develop targeted therapeutic approaches for Golgi dysfunction-associated conditions. Furthermore, its exploration is an example of scientific progress while simultaneously offering hope for developing innovative treatments for neurodegenerative disorders.

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The Regulation of Rab GTPases by Phosphorylation

Cited by 19 publications

References 91 publications

Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian

Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian

Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport

The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

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