The role of spartin and its novel ubiquitin binding region in DALIS occurrence

Karlsson, Amelia; Washington, Jacqueline; Dimitrova, Valentina; Hooper, Christopher; Shekhtman, Alexander; Bakowska, Joanna C.

doi:10.1091/mbc.e13-11-0705

Cited by 15 publications

(16 citation statements)

References 49 publications

(87 reference statements)

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“…During the early stages of embryonic development, maximal levels of SPG20 occur in the limbs, face, and forebrain primordial [9]. Spartin is a multifunctional protein encoded by SPG20, which plays a roles in the dendritic aggresome-like induced structures (DALIS) formation through a ubiquitin-binding region (UBR) [8], lipid droplet formation [4]. The N-terminal region of spartin, which contain microtubule interacting domain (MIT), shares sequence similarity to the MIT domain in the spastin (SPAST; OMIM 604277, mutated in autosomal dominant spastic paraplegia type 4) and plays a role in cytokinesis [14,16].…”

Section: Discussionmentioning

confidence: 99%

Recurrent null mutation in SPG20 leads to Troyer syndrome

Tawamie

Wohlleber

Uebe

et al. 2015

Molecular and Cellular Probes

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Section: Discussionmentioning

confidence: 99%

Recurrent null mutation in SPG20 leads to Troyer syndrome

Tawamie

Wohlleber

Uebe

et al. 2015

Molecular and Cellular Probes

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“…Given that knockdown of Spartin induces the accumulation of lipid droplets, WWP1 might be expected to regulate droplet size through Spartin monoubiquitylation, although such regulation has not yet been shown. Interestingly, a recent study showed that Spartin directly binds to mono-and diubiquitin as well as localizes to another subcellular compartment, DALIS (dendritic aggresome-like induced structures), in lipopolysaccharide-stimulated macrophages (Karlsson et al 2014). It was not examined whether monoubiquitylation inhibits the ubiquitin binding function of Spartin or its ability to localize to DALIS in a manner similar to that operative for endocytic adaptor proteins.…”

Section: Regulation Of Membrane-associated Processes By Monoubiquitylmentioning

confidence: 99%

Protein monoubiquitylation: targets and diverse functions

Nakagawa

Nakayama

2015

Genes to Cells

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Ubiquitin is a 76‐amino acid protein whose conjugation to protein targets is a form of post‐translational modification. Protein ubiquitylation is characterized by the covalent attachment of the COOH‐terminal carboxyl group of ubiquitin to an amino group of the substrate protein. Given that the NH2‐terminal amino group is usually masked, internal lysine residues are most often targeted for ubiquitylation. Polyubiquitylation refers to the formation of a polyubiquitin chain on the substrate as a result of the ubiquitylation of conjugated ubiquitin. The structures of such polyubiquitin chains depend on the specific lysine residues of ubiquitin targeted for ubiquitylation. Most of the polyubiquitin chains other than those linked via lysine‐63 and methionine‐1 of ubiquitin are recognized by the proteasome and serve as a trigger for substrate degradation. In contrast, polyubiquitin chains linked via lysine‐63 and methionine‐1 serve as a binding platform for proteins that function in immune signal transduction or DNA repair. With the exception of a few targets such as histones, the functions of protein monoubiquitylation have remained less clear. However, recent proteomics analysis has shown that monoubiquitylation occurs more frequently than polyubiquitylation, and studies are beginning to provide insight into its biologically important functions. Here, we summarize recent findings on protein monoubiquitylation to provide an overview of the targets and molecular functions of this modification.

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“…SPG20 is located at 13q13.3 and contains 14 exons that encode the spartin protein. Spartin consists of 666 amino acids and is involved in microtubule interaction and trafficking through its MIT domain, and contains a ubiquitin‐binding region and a plant‐related senescence domain . Spartin is mainly localized in endosomes, middle bodies, lipid droplets, and mitochondria .…”

Section: Introductionmentioning

confidence: 99%

“…Spartin consists of 666 amino acids and is involved in microtubule interaction and trafficking through its MIT domain, and contains a ubiquitin-binding region and a plantrelated senescence domain. 5 Spartin is mainly localized in endosomes, middle bodies, lipid droplets, and mitochondria. 6,7 Spartin has different expression levels in various tissues and organs, and it is highly expressed in the temporal lobe, anterior central gyrus, corpus callosum, adipose tissue, and the placenta.…”

Section: Introductionmentioning

confidence: 99%

Dwarfism in Troyer syndrome: a family with SPG20 compound heterozygous mutations and a literature review

Liang

Miao

Yang

et al. 2019

Annals of the New York Academy of Sciences

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Troyer syndrome is an autosomal recessive disease characterized by spastic paralysis, dysarthria, distal amyotrophy, and short stature. Recently, two siblings (an older brother and a younger sister) were admitted to our hospital for the chief complaints of “short stature and intellectual disability.” Through whole exome sequencing of the sister, who is the proband, it was found that her SPG20 gene had compound heterozygous mutations: c.364_365delAT (p.Met122Valfs*2) and c.892delA (p.Thr298Glnfs*30). Target testing revealed that the brother had the same genotype as the sister, and the former mutation originated from the father, while the latter mutation originated from the mother. In summary, this is the first report of Troyer syndrome in a family caused by SPG20 compound heterozygous mutations. A novel SPG20 mutation was found, namely c.892delA (p.Thr298Glnfs*30). In addition, we also summarize these Troyer syndrome patients’ heights and their clinical characteristics, and provide a brief review of all known pathogenic mutations of SPG20.

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The role of spartin and its novel ubiquitin binding region in DALIS occurrence

Abstract: Spartin contributes to the formation of dendritic aggresome-like induced structures (DALIS) through a unique ubiquitin-binding region (UBR). Using NMR and in vitro binding, the authors characterize spartin's UBR and show that DALIS formation depends on key residues within its UBR.

Cited by 15 publications

References 49 publications

Recurrent null mutation in SPG20 leads to Troyer syndrome

Recurrent null mutation in SPG20 leads to Troyer syndrome

Protein monoubiquitylation: targets and diverse functions

Dwarfism in Troyer syndrome: a family with SPG20 compound heterozygous mutations and a literature review

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