VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and function

Publication date: May 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 5, Part A Author(s): Clare Rogerson, Paul Gissen Mutations in VPS33B and VIPAS39 cause the severe multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome. Amongst other symptoms, patients with ARC syndrome suffer from severe ichthyosis. Roles for VPS33B and VIPAR have been reported in lysosome-related organelle biogenesis, integrin recycling, collagen homeostasis and maintenance of cell polarity. Mouse knockouts of Vps33b or Vipas39 are good models of ARC syndrome and develop an ichthyotic phenotype. We demonstrate that the skin manifestations in Vps33b and Vipar deficient mice are histologically similar to those of patients with ARC syndrome. Histological, immunofluorescent and electron microscopic analysis of Vps33b and Vipar deficient mouse skin biopsies and isolated primary cells showed that epidermal lamellar bodies, which are essential for skin barrier function, had abnormal morphology and the localisation of lamellar body cargo was disrupted. Stratum corneum formation was affected, with increased corneocyte thickness, decreased thickness of the cornified envelope and reduced deposition of lipids. These defects impact epidermal homeostasis and lead to abnormal barrier formation causing the skin phenotype in Vps33b and Vipar deficient mice and patients with ARC syndrome.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Source: Der Hautarzt: Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete - Category: Dermatology Tags: Hautarzt Source Type: research
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Three Austrian patients presented with severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness. Exome sequencing revealed biallelic mutations in VPS33B, encoding VPS33B, a Sec1/Munc18 family protein which interacts with Rab11a and Rab25 proteins and is involved in trafficking of the collagen modifying enzyme LH3. Two patients showed the homozygous missense variant p.Gly131Glu, whilst one patient was compound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in patients with arthrogryposis renal dysfunction and cholestasis syndrome.
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Mutations in Vps33b and Vipas39 cause the rare multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome (ARC); one characteristic but understudied feature of which is severe ichthyosis. The Vps33b and Vipar proteins interact and have been shown to also interact with Rab GTPases and act as a tethering factor; the class C Homologues in Endosome-Vesicle Interaction (CHEVI) complex. ARC syndrome patients have been shown to have entombed lamellar body-like structures in the stratum corneum however the molecular mechanisms underlying ARC patient ichthyosis and the specific role of the CHEVI complex in the ...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Epidermal Structure and Barrier Function Source Type: research
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More News: Cholestasis | Ichthyosis | Skin | Skin Biopsy