ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita

Abumansour, Iman S.; Hijazi, Hadia; Alazmi, Anas; Alzahrani, Fatma; Bashiri, Fahad A.; Hassan, Hamdy H.; Al-Haddab, Mohammed; Alkuraya, Fowzan S.

doi:10.1007/s00439-015-1561-6

Cited by 19 publications

(15 citation statements)

References 15 publications

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“…Arl6ip6 is a susceptibility locus for ischemic stroke [53]. It lacks enzyme-related domains, but does show physical interactions in proteome-wide pull-down screens with a number of proteins involved in membrane vesicle formation/targeting [33,54], a process that is involved in NE resealing and repair.…”

Section: Discussionmentioning

confidence: 99%

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Cheng

Baboo

Lindsay

et al. 2018

Preprint

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The nuclear envelope (NE) is an endoplasmic reticulum (ER) subdomain that contains characteristic components dedicated to nuclear functions. These include nuclear pore complexes (NPCs) -the channels for nucleocytoplasmic transport, and the nuclear lamina (NL) -a scaffold for NE and chromatin organization at the nuclear periphery. Since numerous human diseases associated with NE/NL proteins occur in mesenchyme-derived cells, a more comprehensive characterization of proteins concentrated at the NE in these cell types is warranted. Accordingly, we used proteomics to analyze NE and other subcellular fractions isolated from mesenchymal stem cells and from differentiated adipocytes and myocytes. We evaluated the proteomics datasets to calculate relative protein enrichment in the NE fraction, using a spectral abundance-based scoring system that accurately described most benchmark proteins. We then examined five high-scoring transmembrane proteins expressed in all three cell types that were not previously known to be enriched at the NE. Using quantitative immunofluorescence microscopy to track ectopically expressed proteins, we validated that all five of these components are substantially concentrated at the NE of multiple cell types. One (Itprip) is exposed to the outer nuclear membrane, a second (Smpd4) is enriched at the NPC, and the three others (Mfsd10, Tmx4, and Arl6ip6) are suggested to reside in the inner nuclear membrane. Considering their sequences and other features, these proteins provide new focal points for studying the functions and membrane dynamics of the NE. Our datasets should be useful for identifying additional NE-concentrated proteins, and for evaluating candidates that are identified in screening.

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Section: Discussionmentioning

confidence: 99%

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Cheng

Baboo

Lindsay

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…This suggests a potential role in regulating the luminal aspects of NE specific structures, such as the LINC complex and associated torsinA, both of which may be regulated by disulfide oxidation/reduction [52,53]. Arl6ip6 is a susceptibility locus for ischemic stroke [54]. It lacks enzymerelated domains, but does show physical interactions in proteome-wide pull-down screens with a number of proteins involved in membrane vesicle formation/targeting [33,55], a process that is involved in NE resealing and repair.…”

Section: V5-arl6ip6mentioning

confidence: 99%

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Cheng

Baboo

Lindsay

et al. 2019

Nucleus

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The double membrane nuclear envelope (NE), which is contiguous with the ER, contains nuclear pore complexes (NPCs) – the channels for nucleocytoplasmic transport, and the nuclear lamina (NL) – a scaffold for NE and chromatin organization. Since numerous human diseases linked to NE proteins occur in mesenchyme-derived cells, we used proteomics to characterize NE and other subcellular fractions isolated from mesenchymal stem cells and from adipocytes and myocytes. Based on spectral abundance, we calculated enrichment scores for proteins in the NE fractions. We demonstrated by quantitative immunofluorescence microscopy that five little-characterized proteins with high enrichment scores are substantially concentrated at the NE, with Itprip exposed at the outer nuclear membrane, Smpd4 enriched at the NPC, and Mfsd10, Tmx4, and Arl6ip6 likely residing in the inner nuclear membrane. These proteins provide new focal points for studying the functions of the NE. Moreover, our datasets provide a resource for evaluating additional potential NE proteins.

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“…The pathogenesis of CMTC remains multifactorial. Homozygous truncating mutation in ARL6IP6 with syndromic form has been reported as a possible genetic cause for CMTC 2. However, there is no family history of vascular anomalies in the family of the reported case.…”

Section: Descriptionmentioning

confidence: 84%

Cutis marmorata telangiectatica congenita with skin ulceration: a rare benign skin vascular malformation

Jia

Rajadurai

Chandran³

2018

BMJ Case Reports

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ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita

Cited by 19 publications

References 15 publications

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells

Cutis marmorata telangiectatica congenita with skin ulceration: a rare benign skin vascular malformation

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