Rab13 Regulates Neurite Outgrowth in PC12 Cells through Its Effector Protein, JRAB/MICAL-L2

Sakane, Ayuko; Honda, Kazufumi; Sasaki, Takuya

doi:10.1128/mcb.01067-09

Cited by 72 publications

(89 citation statements)

References 26 publications

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“…Rab13, a Rab closely related to Rab8 and Rab10, is reported to be necessary for neurite elongation (Sakane et al, 2010). Additionally, Rab17 and Rab22, which belong to different subfamilies of Rab8, have been reported to be necessary for dendrite (Mori et al, 2012) and neurite elongation (Wang et al, 2011a), respectively.…”

Section: Discussionmentioning

confidence: 99%

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Satō¹,

Iwano²,

Kunii³

et al. 2014

Development

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The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis.

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Section: Discussionmentioning

confidence: 99%

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Satō¹,

Iwano²,

Kunii³

et al. 2014

Development

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“…Previous studies showed that some bMERB domain containing effector proteins form an auto-inhibited state in which the bMERB domain binds to the actin-binding CH-domain and inhibit its interaction with actin. Thus, bMERB domains might contain one Rab-binding site for recruitment and one for release of the auto-inhibition (Schmidt et al, 2008;Sakane et al, 2010;Sun et al, 2016). It is also possible that the domains might simultaneously bind two different Rabs and act as sorting hubs in endosomal trafficking.…”

Section: Bivalent Monomeric Rab Effectors (Bmerbs; Bivalent Mical/ehmentioning

confidence: 99%

Mechanisms of action of Rab proteins, key regulators of intracellular vesicular transport

Goody

Müller

2016

Biological Chemistry

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Our understanding of the manner in which Rab proteins regulate intracellular vesicular transport has progressed remarkably in the last one or two decades by application of a wide spectrum of biochemical, biophysical and cell biological methods, augmented by the methods of chemical biology. Important additional insights have arisen from examination of the manner in which certain bacteria can manipulate vesicular transport mechanisms. The progress in these areas is summarized here.

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“…Consistently, filamin levels also correlate with invasiveness of melanoma cell lines, and high filamin levels are predictive of poor prognosis in melanoma patients (77). Interestingly, in the absence of Rab13, MICAL-L2 and actinin-4 promote cell-cell adhesion by stimulating thick actin bundling at the cell periphery (44,45). Consistently, high levels of actinin-4 are associated with decreased cell motility (78,79).…”

Section: Cell Migration and Scatteringmentioning

confidence: 55%

“…Insulin stimulation increases the pool of active Rab13, which binds to the Rab13 effector MICAL-L2, relieving MICAL-L2 auto-inhibition and thus allowing MICAL-L2 to recruit various actin regulatory proteins including actinin-4 ( Fig. 2) (5,44,45). A complex involving Rab13, MICAL-L2, and actinin-4 binds to GLUT4 in an insulindependent manner, allowing docking/tethering of GLUT4 vesicles at the cell surface and thus enabling their fusion (46).…”

Section: Cell Metabolismmentioning

confidence: 99%

Regulation of Cancer Cell Behavior by the Small GTPase Rab13

Ioannou

McPherson

2016

Journal of Biological Chemistry

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The members of the Rab family of GTPases are master regulators of cellular membrane trafficking. With ϳ70 members in humans, Rabs have been implicated in all steps of membrane trafficking ranging from vesicle formation and transport to vesicle docking/tethering and fusion. Vesicle trafficking controls the localization and levels of a myriad of proteins, thus regulating cellular functions including proliferation, metabolism, cellcell adhesion, and cell migration. It is therefore not surprising that impairment of Rab pathways is associated with diseases including cancer. In this review, we highlight evidence supporting the role of Rab13 as a potent driver of cancer progression.The members of the Rab (Ras-related in brain) family of proteins are master regulators of vesicle trafficking. They are evolutionarily conserved with ϳ70 members in humans, and each Rab is localized predominantly to a specific intracellular organelle or vesicle (1). Rabs have been implicated in every step of vesicle trafficking including the formation of cargo-laden membrane vesicles and tubules, transport of these carriers on the cytoskeleton, tethering and docking of the carriers at the target membrane, and finally membrane fusion and delivery of cargo. Not surprisingly, functional impairment of Rab pathways is associated with diseases including immunodeficiencies, neurological disorders, and cancer (2). One such Rab, Rab13, controls cellular functions that are often altered in cancer, and Rab13 is now recognized as an important driver of cancer progression. Here, we discuss the importance of Rab13 in the physiology of cancer with a focus on Rab13 trafficking pathways contributing to tumorigenicity. The Biology of Rab13As for all small GTPases, Rab13 cycles between an active, GTP-bound state and an inactive, GDP-bound state. Activation of Rab13 is mediated by DENND2B and DENND1C/connecdenn 3, guanine nucleotide exchange factors (GEFs) 2 that interact with GDP-bound Rab13 and facilitate the exchange of GDP for GTP (3-5). These proteins each bear a differentially expressed in normal and neoplastic cells (DENN) domain, an evolutionarily ancient protein module that encodes GEF activity for a large number of Rab GTPases (6 -8). Rab13 is inactivated by the GTPase-activating protein (GAP) Akt substrate 160 (AS160)/TBC1D4, which enhances the ability of Rab13 to hydrolyze GTP (3-5). In its active form, Rab13 binds to several effectors including MICAL-L1, MICAL-L2, and PKA (9, 10). Rab13, which is ubiquitously expressed, is thought to have diverged from its closest homologue Rab8, early in the vertebrate lineage (11). Similar to Rab8, Rab13 has been implicated in both biosynthetic and endosomal recycling pathways. Rab13 is found at the trans-Golgi network, on recycling endosomes, on late endosomes, and at the plasma membrane (12-14). Disruption of Rab13 function inhibits the delivery of cargo that reaches the plasma membrane via endosomes from either the biosynthetic or the endocytic recycling pathways. Thus, Rab13 is thought to control membrane t...

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Rab13 Regulates Neurite Outgrowth in PC12 Cells through Its Effector Protein, JRAB/MICAL-L2

Cited by 72 publications

References 26 publications

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

Mechanisms of action of Rab proteins, key regulators of intracellular vesicular transport

Regulation of Cancer Cell Behavior by the Small GTPase Rab13

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