Microtubule-associated protein 8 contains two microtubule binding sites

Ding, Jingzhong; Valle, Angela; Allen, Elizabeth; Wang, Wei; Nardine, Timothy; Zhang, Yingjiu; Peng, Linfeng; Yang, Yanmin

doi:10.1016/j.bbrc.2005.10.199

Cited by 12 publications

(18 citation statements)

References 30 publications

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“…Taken together, these studies provide strong support to the notion that MAP1B expression is under exquisite control. MAP8/MAP1S is a recently identified MAP containing two microtubule-binding sites [53]. The protein is translated from a single transcript, and cleaved posttranslationally into a 100-kDa heavy (HC) and 25-kDa light (LC) chain [53,54].…”

Section: Pathogenesismentioning

confidence: 99%

Giant axonal neuropathy

Yang

Allen

Ding

et al. 2007

Cell. Mol. Life Sci.

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Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder affecting both the central and peripheral nervous systems. Cytopathologically, the disorder is characterized by giant axons with derangements of cytoskeletal components. Geneticists refined the chromosomal interval containing the locus, culminating in the cloning of the defective gene, GAN. To date, many distinct mutations scattered throughout the coding region of the locus have been reported by researchers from different groups around the world. GAN encodes the protein, gigaxonin. Recently, a genetic mouse model of the disease was generated by targeted disruption of the locus. Over the years, the molecular mechanisms underlying GAN have attracted much interest. Studies have revealed that gigaxonin appears to play an important role in cytoskeletal functions and dynamics by directing ubiquitin-mediated degradations of cytoskeletal proteins. Aberrant accumulations of cytoskeletal-associated proteins caused by a defect in the ubiquitin-proteasome system (UPS) have been shown to be responsible for neurodegeneration occurring in GAN-null neurons, providing strong support for the notion that UPS plays crucial roles in cytoskeletal functions and dynamics. However, many key questions about the disease remain unanswered.

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Section: Pathogenesismentioning

confidence: 99%

Giant axonal neuropathy

Yang

Allen

Ding

et al. 2007

Cell. Mol. Life Sci.

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“…It also carried the names such as variably charged protein Y2 (VCY2) interacting protein 1 (VCY2IP-1) (16), basic protein on Y chromosome 2 (BPY2) interacting protein 1 (BPY2IP1) (16), ras association domain family 1 (RASSF1)-binding protein 1 (RABP1) (17), and microtubule-associated protein 8 (MAP8) (18). It is a widely distributed homologue of neuron-specific MAP1A and MAP1B (15,19,20).…”

mentioning

confidence: 99%

Microtubule-associated Protein 1S (MAP1S) Bridges Autophagic Components with Microtubules and Mitochondria to Affect Autophagosomal Biogenesis and Degradation

Xie

Nguyen

McKeehan

et al. 2011

Journal of Biological Chemistry

113

165

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The ubiquitously distributed MAP1S is a homologue of the exclusively neuronal distributed microtubule-associated protein 1A and 1B (MAP1A/B). They give rise to multiple isoforms through similar post-translational modification. Isoforms of MAP1S have been implicated in microtubule dynamics and mitotic abnormalities and mitotic cell death. Here we show that ablation of the Map1s gene in mice caused reduction in the B-cell CLL/lymphoma 2 or xL (Bcl-2/xL) and cyclin-dependent kinase inhibitor 1B (P27) protein levels, accumulation of defective mitochondria, and severe defects in response to nutritive stress, suggesting defects in autophagosomal biogenesis and clearance. Furthermore, MAP1S isoforms interacted with the autophagosome-associated light chain 3 of MAP1A/B (LC3), a homologue of yeast autophagy-related gene 8 (ATG8), and recruited it to stable microtubules in a MAP1S and LC3 isoformdependent mode. In addition, MAP1S interacted with mitochondrion-associated leucine-rich PPR-motif containing protein (LRPPRC) that interacts with the mitophagy initiator and Parkinson disease-related protein Parkin. The three-way interactions of MAP1S isoforms with LC3 and microtubules as well as the interaction of MAP1S with LRPPRC suggest that MAP1S isoforms may play positive roles in integration of autophagic components with microtubules and mitochondria in both autophagosomal biogenesis and degradation. For the first time, our results clarify roles of MAP1S in bridging microtubules and mitochondria with autophagic and mitophagic initiation, maturation, trafficking, and lysosomal clearance. Defects in the MAP1S-regulated autophagy may impact heart disease, cancers, neurodegenerative diseases, and a wide range of other diseases.Autophagy, or self-digestion, is a process that begins with the formation of isolation membranes that engulf substrates to form autophagosomes. Then autophagosomes fuse with lysosomes to generate autolysosomes in which substrates are degraded (1). The initiation of autophagy is regulated by the mammalian target of rapamycin (mTOR) pathway. Autophagy will be shut down through either the phosphatidylinositol 3-kinase (PI3K)-v-akt murine thymoma viral oncogene (AKT)-mTOR pathway in response to signals from growth factors or the serine/threonine kinase 11 (LKB1)-AMP-activated protein kinase (AMPK) 2 -mTOR pathway in response to signals from nutrients and metabolites. The anti-apoptotic protein Bcl-2 and Bcl-xL exhibit opposite functions in autophagy initiation. They inhibit autophagy initiation through the PI3K-AKTmTOR pathway by sequestering the BCL2 interacting protein (Beclin 1) or activate autophagy initiation through the LKB1-AMPK-mTOR pathway by increasing P27 levels (2, 3).After initiation, the metabolism of LC3 has emerged as a key biochemical marker for tracking of autophagy and autophagosomes (4, 5). The 22-kDa full-length LC3 (4) is proteolytically modified into LC3I form by ATG4, resulting in exposure of a C-terminal glycine (5). LC3I is first conjugated with the ubiquitin activating enzyme (E1)-...

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“…Based on C19ORF5 localization and ability to bind to the microtubules (20,23), we hypothesized that the mitotic problems associated with C19ORF5 depletion result from aberrant microtubule dynamics. We have found that the spindle is abnormal throughout mitosis in C19ORF5-depleted cells.…”

Section: Discussionmentioning

confidence: 99%

“…C19ORF5, as well as its other interacting partner, LRP130, can bind nucleic acids although the function of this binding is not clear (22). Despite the existence of two conserved microtubule-binding regions in C19ORF5 (23,24), the overexpressed protein exhibits diffused cytosolic staining patterns. C19ORF5 association with the microtubules becomes more evident when cells are treated with the microtubule-stabilizing drug paclitaxel or when C19ORF5 is coexpressed with RASSF1A (14,25).…”

Section: Introductionmentioning

confidence: 99%

Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities

et al. 2007

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Ras association domain family 1, isoform A (RASSF1A) is a novel tumor suppressor gene that is found to be inactivated in more than 40 types of sporadic cancers. In addition, mouse Rassf1a knockout models have an increased frequency of spontaneous and induced tumors. The mechanisms by which RASSF1A exerts its tumor suppression activities or the pathways it can regulate are not yet fully understood. Using yeast two-hybrid system, we have previously identified C19ORF5/MAP1S as the major RASSF1A-interacting protein.C19ORF5 has two conserved microtubule-associated regions and may function to anchor RASSF1A to the centrosomes. In this study, we have analyzed the cellular functions of C19ORF5. By using small interfering RNA-mediated depletion and time-lapse video microscopy, we show that C19ORF5 knockdown causes mitotic abnormalities that consist of failure to form a stable metaphase plate, premature sister chromatid separation, lagging chromosomes, and multipolar spindles. We also show that a fraction of C19ORF5 localizes to the spindle microtubules. Additionally, we show here that C19ORF5 localizes to the microtubule-organizing centers during microtubule regrowth after nocodazole washout. Knockdown of C19ORF5 disrupts the microtubule-organizing center and results in microtubule nucleation from several sites. Whereas the localization of pericentrin is not affected, A-and ;-tubulin localization and sites of nucleation are greatly altered by C19ORF5 depletion. This may indicate that C19ORF5 plays a role in anchoring the microtubuleorganizing center to the centrosomes. In addition, we show that the NH 2 terminus of C19ORF5 is essential for this process. This novel role for C19ORF5 could explain the resulting mitotic abnormalities that occur on its depletion and can potentially provide an underlying mechanism for the frequent centrosome and microtubule abnormalities detected in several cancers. [Cancer Res 2007;67(2):492-500]

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Microtubule-associated protein 8 contains two microtubule binding sites

Cited by 12 publications

References 30 publications

Giant axonal neuropathy

Giant axonal neuropathy

Microtubule-associated Protein 1S (MAP1S) Bridges Autophagic Components with Microtubules and Mitochondria to Affect Autophagosomal Biogenesis and Degradation

Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities

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