A common pathomechanism in GMAP-210- and LBR-related diseases.
A common pathomechanism in GMAP-210- and LBR-related diseases.
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GMAP-210 和 LBR 相关疾病的常见病理机制。
DOI：
10.1172/jci.insight.121150
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发表时间：
2018
期刊：
影响因子：
8
通讯作者：
Wehrle A
中科院分区：
文献类型：
--
作者：
Wehrle A
Biallelic loss-of-function mutations in TRIP11, encoding the golgin GMAP-210, cause the lethal human chondrodysplasia achondrogenesis 1A (ACG1A). We now find that a homozygous splice-site mutation of the lamin B receptor (LBR) gene results in the same phenotype. Intrigued by the genetic heterogeneity, we compared GMAP-210– and LBR-deficient primary cells to unravel how particular mutations in LBR cause a phenocopy of ACG1A. We could exclude a regulatory interaction between LBR and GMAP-210 in patients’ cells. However, we discovered a common disruption of Golgi apparatus architecture that was accompanied by decreased secretory trafficking in both cases. Deficiency of Golgi-dependent glycan processing indicated a similar downstream effect of the disease-causing mutations upon Golgi function. Unexpectedly, our results thus point to a common pathogenic mechanism in GMAP-210– and LBR-related diseases attributable to defective secretory trafficking at the Golgi apparatus.
