Analysis of cellular molecules associated with keratinocyte differentiation

我们研究了人体表皮中肽精氨酸脱亚胺酶(PADS)的表达(Cell Mol Life Sci2005)。我们发现PAD1、2和3都有表达。PAD1和PAD3与微丝蛋白共定位。PAD存在到角质上皮细胞，在那里它去氨化角蛋白K1。我们已经证明LEKI定位于板层颗粒中，与KLK5和KLK7分离，并且分泌在表皮中的颗粒浅层的细胞外空间(J Invest Dermatol 2005)。我们还揭示了在缺乏Lekti的Netherton综合征中，颗粒浅层出现异常分裂，这表明Lekti正在防止角质层粘连的过早丧失。我们建立了SPINK5缺陷小鼠作为Netherton综合征的模型。利用这一模型，我们发现桥粒蛋白1降解引起的桥粒裂解是该病的主要致病事件。(自然遗传学2005)。我们描述了一种新的神经皮肤综合征，其特征是脑发育不全、神经病变、鱼鳞病和角皮病(CEDNIK综合征)，由SNAP29基因突变引起，SNAP29编码参与细胞内运输的圈套蛋白(Am J Hum Genet 2005)。在鱼鳞病患者的皮肤中，板层颗粒蛋白的分泌受到抑制。我们发现了板层颗粒蛋白的新成员，即A2ML(α-2巨球蛋白样蛋白)和Dermokin(J Biol Chem，2006，J Invest Dermatol 2006)。

We studied peptidylarginine deiminases (PADs) expression in human epidermis (Cell Mol Life Sci 2005). We found that PAD1,2 and 3 are expressed. PAD1 and PAD3 are co-localized with filaggrin. PAD was present up to the supper corneocytes where it deiminates keratin K1.We have shown that LEKI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum in the epidermis (J Invest Dermatol 2005).We also disclosed that in Netherton syndrome where LEKTI is absent, an abnormal split was seen in the superficial stratum granulosum, suggesting that LEKTI is preventing premature loss of stratum corneum cohesion.We generated SPINK5-deficient mice as a model for Netherton syndrome. Using this model, we showed that desmosome cleavage due to desmoglein 1 degradation is the primary pathogenic event in this disease. (Nature Genetics 2005).We describe a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome) caused by a mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking (Am J Hum Genet 2005). In the ichthyotic patient skin, secretion of lamellar granule proteins was inhibited.We have identified novel members of lamellar granule proteins, namely A2ML (alpha-2 macroglobulin-like) and Dermokin (J Biol Chem, 2006,J Invest Dermatol 2006).