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The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes

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The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. / Cabral, Rita M.; Tattersall, Daniel; Patel, Vishal; McPhail, Graham D.; Hatzimasoura, Elizabeth; Abrams, Dominic J.; South, Andrew P.; Kelsell, David P.

In: Journal of Cell Science, Vol. 125, No. 12, 15.06.2012, p. 2853-2861.

Research output: Contribution to journalArticle

Harvard

Cabral, RM, Tattersall, D, Patel, V, McPhail, GD, Hatzimasoura, E, Abrams, DJ, South, AP & Kelsell, DP 2012, 'The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes' Journal of Cell Science, vol 125, no. 12, pp. 2853-2861., 10.1242/jcs.084152

APA

Cabral, R. M., Tattersall, D., Patel, V., McPhail, G. D., Hatzimasoura, E., Abrams, D. J., ... Kelsell, D. P. (2012). The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. Journal of Cell Science, 125(12), 2853-2861. 10.1242/jcs.084152

Vancouver

Cabral RM, Tattersall D, Patel V, McPhail GD, Hatzimasoura E, Abrams DJ et al. The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes. Journal of Cell Science. 2012 Jun 15;125(12):2853-2861. Available from: 10.1242/jcs.084152

Author

Cabral, Rita M.; Tattersall, Daniel; Patel, Vishal; McPhail, Graham D.; Hatzimasoura, Elizabeth; Abrams, Dominic J.; South, Andrew P.; Kelsell, David P. / The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes.

In: Journal of Cell Science, Vol. 125, No. 12, 15.06.2012, p. 2853-2861.

Research output: Contribution to journalArticle

Bibtex - Download

@article{6c01bcecd43143cbbf9f2181166836b8,
title = "The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes",
author = "Cabral, {Rita M.} and Daniel Tattersall and Vishal Patel and McPhail, {Graham D.} and Elizabeth Hatzimasoura and Abrams, {Dominic J.} and South, {Andrew P.} and Kelsell, {David P.}",
year = "2012",
doi = "10.1242/jcs.084152",
volume = "125",
number = "12",
pages = "2853--2861",
journal = "Journal of Cell Science",
issn = "0021-9533",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT keratinocytes

A1 - Cabral,Rita M.

A1 - Tattersall,Daniel

A1 - Patel,Vishal

A1 - McPhail,Graham D.

A1 - Hatzimasoura,Elizabeth

A1 - Abrams,Dominic J.

A1 - South,Andrew P.

A1 - Kelsell,David P.

AU - Cabral,Rita M.

AU - Tattersall,Daniel

AU - Patel,Vishal

AU - McPhail,Graham D.

AU - Hatzimasoura,Elizabeth

AU - Abrams,Dominic J.

AU - South,Andrew P.

AU - Kelsell,David P.

PY - 2012/6/15

Y1 - 2012/6/15

N2 - <p>Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have different disease-causing molecular mechanisms as evidenced by the varying phenotypes resulting from mutations affecting different domains of the same protein, but the majority of these mechanisms remain to be determined. Here, we studied two mutations in DSP that lead to different dosages of the two major DSP splice variants, DSPI and DSPII, and compared their molecular mechanisms. One of the mutations results in total DSP haploinsufficiency and is associated with autosomal dominant striate palmoplantar keratoderma (PPK). The other leads to complete absence of DSPI and the minor isoform DSPIa but normal levels of DSPII, and is associated with autosomal recessive epidermolytic PPK, woolly hair and severe arrhythmogenic dilated cardiomyopathy. Using siRNA treatments to mimic these two mutations and additionally a DSPII-specific siRNA, we found striking differences between DSP isoforms with respect to keratinocyte adhesion upon cellular stress with DSPII being the key component in intermediate filament (IF) stability and desmosome-mediated adhesion. In addition, reduction in DSP expression reduced the amount of plakophilin 1, desmocollin (DSC) 2 and DSC3 with DSPI having a greater influence than DSPII on the expression levels of DSC3. These results suggest that the two major DSP splice variants are not completely redundant in function and that DSPII dosage is particularly important for desmosomal adhesion in the skin.</p>

AB - <p>Desmosomes are intercellular junctions specialised for strong adhesion that are prominent in the epidermis and heart muscle. Defective desmosomal function due to inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes skin or heart disorders and in some instances both. Different mutations have different disease-causing molecular mechanisms as evidenced by the varying phenotypes resulting from mutations affecting different domains of the same protein, but the majority of these mechanisms remain to be determined. Here, we studied two mutations in DSP that lead to different dosages of the two major DSP splice variants, DSPI and DSPII, and compared their molecular mechanisms. One of the mutations results in total DSP haploinsufficiency and is associated with autosomal dominant striate palmoplantar keratoderma (PPK). The other leads to complete absence of DSPI and the minor isoform DSPIa but normal levels of DSPII, and is associated with autosomal recessive epidermolytic PPK, woolly hair and severe arrhythmogenic dilated cardiomyopathy. Using siRNA treatments to mimic these two mutations and additionally a DSPII-specific siRNA, we found striking differences between DSP isoforms with respect to keratinocyte adhesion upon cellular stress with DSPII being the key component in intermediate filament (IF) stability and desmosome-mediated adhesion. In addition, reduction in DSP expression reduced the amount of plakophilin 1, desmocollin (DSC) 2 and DSC3 with DSPI having a greater influence than DSPII on the expression levels of DSC3. These results suggest that the two major DSP splice variants are not completely redundant in function and that DSPII dosage is particularly important for desmosomal adhesion in the skin.</p>

U2 - 10.1242/jcs.084152

DO - 10.1242/jcs.084152

M1 - Article

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 12

VL - 125

SP - 2853

EP - 2861

ER -

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