Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.
Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.
复制标题
整联蛋白α3β1在局灶性粘连中的不同功能和α6β4/bullous子型抗原抗原在新的稳定锚定接触（SAC）的角质形成细胞中：与Hemidesmosmosys的关系。
DOI：
10.1083/jcb.111.6.3141
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发表时间：
1990-12
影响因子：
7.8
通讯作者：
Wayner, E A
中科院分区：
文献类型：
--
作者：
Carter, W G;Kaur, P;Gil, S G;Gahr, P J;Wayner, E A
复层表皮的基底细胞通过半桥粒固定在皮肤的基底膜带(BMZ)。我们先前在培养的人角质形成细胞(HFK)的焦点黏附(FAs)中发现整合素α3β1是HfK与分泌的BMZ样细胞外基质(ECM；Carter，W.G.，E.A.Wayner，T.S.Bouchard和P.Kaur)黏附的介体。1990年。J.细胞生物学。110：1387-1404)。在这里，我们研究了整合素α6β4和α3β1与大疱性类天疱疮抗原(BPA)的关系，BPA是半桥粒的一个组成部分。我们得出结论，HFKs中的α6β4定位于一种新的稳定锚定接触(SAC)中，该接触与α3β1-FAs协同介导与ECM的黏附。(A)将分泌的ECM与外源层粘连蛋白、纤维连接蛋白和胶原进行比较，发现ECM是HfK黏附和铺展以及α6β4囊和α3β1 FAs形成的首选配体。(2)抗-α3-β1(P1B5)和抗-α-6-β4(GoH3)联合抗体抑制HfK与ECM的黏附，表明两种受体均具有与ECM黏附的功能，而α-3-β1对ECM的黏附起主导作用。(C)α-6-β-4与BPA共定位于FAs近端但不在FAs外的囊中。抗体排斥和干涉反射显微镜显示，α6β4-SAs和α3β1-FAs均与粘附面接触。(D)与α3β1-FAs相反，α6β4-SAs仅存在于非运动细胞中，与应激纤维无关，对洗涤剂和尿素相对稳定，提示对SAs具有非运动性或锚定功能，而对α3β1-FAs具有运动功能。(E)在亲和分离过程中，α6β4与外源性ECM形成不溶于洗涤剂的复合体，证实了一种未知的ECM配体与α6β4相互作用的能力。(F)我们认为培养中的α6β4/BPA-SAs限制HFKs在ECM上的迁移，而α3β1-FA在铺展和迁移细胞中形成动态黏附。培养中的α-6-β-4/BPA-囊在功能和组成上与皮肤中的半桥粒相似。
Basal cells of stratified epidermis are anchored to the basement membrane zone (BMZ) of skin via hemidesmosomes. We previously identified integrin alpha 3 beta 1, in focal adhesions (FAs), of cultured human keratinocytes (HFKs) as a mediator of HFK adhesion to secreted BMZ-like extracellular matrix (ECM; Carter, W.G., E.A. Wayner, T.S. Bouchard, and P. Kaur. 1990. J. Cell Biol. 110: 1387-1404). Here, we have examined the relation of integrins alpha 6 beta 4 and alpha 3 beta 1, to bullous pemphigoid antigen (BPA), a component of hemidesmosomes. We conclude that alpha 6 beta 4 in HFKs localizes in a new stable anchoring contact (SAC) that cooperates with alpha 3 beta 1- FAs to mediate adhesion to ECM, based on the following. (a) Comparison of secreted ECM, with exogenous laminin, fibronectin and collagen identified ECM as the preferred ligand for HFK adhesion and spreading and for formation of both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs. (b) Inhibition of HFK adhesion with combined anti-alpha 3 beta 1 (P1B5) and anti-alpha 6 beta 4 (GoH3) antibodies indicated that both receptors were functional in adhesion to ECM while alpha 3 beta 1 played a dominant role in spreading. (c) alpha 6 beta 4 colocalized with BPA in SACs that were proximal to but excluded from FAs. Both alpha 6 beta 4- SACs and alpha 3 beta 1-FAs were in contact with the adhesion surface as indicated by antibody exclusion and interference reflection microscopy. (d) In contrast to alpha 3 beta 1-FAs, alpha 6 beta 4-SACs were present only in nonmotile cells, not associated with stress fibers, and were relatively stable to detergents and urea, suggesting a nonmotile, or anchoring function for SACs and motility functions for alpha 3 beta 1-FAs. (e) alpha 6 beta 4 formed a detergent-insoluble complex with exogenous ECM in an affinity isolation procedure, confirming the ability of an unidentified ECM ligand to interact with alpha 6 beta 4. (f) We suggest that alpha 6 beta 4/BPA-SACs in culture restrict migration of HFKs on ECM while alpha 3 beta 1-FAs form dynamic adhesions in spreading and migrating cells. alpha 6 beta 4/BPA-SACs in culture bear functional and compositional similarities to hemidesmosomes in skin.