The kindlins at a glance

Max Planck Institute of Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18a, Martinsried, 82152, Germany.
Journal of Cell Science (Impact Factor: 5.43). 07/2010; 123(Pt 14):2353-6. DOI: 10.1242/jcs.064600
Source: PubMed

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    • "Main cell surface mediators of those cell matrix interactions are í µí»¼-/í µí»½-dystroglycan [41] [42] [43] [44], syndecans [29, 45–47], and certain integrins being members of a large family of heterodimeric transmembrane proteins ([48] [49] [50] [51]; for general review: [19]). Integrins are intracellularly associated via adapter proteins with actin microfilaments, which is crucial for both cell adhesion and migration, becoming particularly apparent in tumor invasion and metastasis ([52] [53]; reviewed by [54]), and ECM-mediated signalling [55] [56] [57] [58] [59]. The only exception is integrin í µí»¼6í µí»½4 which is normally connected to the basal part of the keratin network via the long cytoplasmic tail of the í µí»½4 subunit and internal plaque proteins (outlined later). "
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    ABSTRACT: The epidermis functions in skin as first defense line or barrier against environmental impacts, resting on extracellular matrix (ECM) of the dermis underneath. Both compartments are connected by the basement membrane (BM), composed of a set of distinct glycoproteins and proteoglycans. Herein we are reviewing molecular aspects of BM structure, composition, and function regarding not only (i) the dermoepidermal interface but also (ii) the resident microvasculature, primarily focusing on the per se nonscaffold forming components perlecan and nidogen-1 and nidogen-2. Depletion or functional deficiencies of any BM component are lethal at some stage of development or around birth, though BM defects vary between organs and tissues. Lethality problems were overcome by developmental stage- and skin-specific gene targeting or by cell grafting and organotypic (3D) cocultures of normal or defective cells, which allows recapitulating BM formation de novo. Thus, evidence is accumulating that BM assembly and turnover rely on mechanical properties and composition of the adjacent ECM and the dynamics of molecular assembly, including further "minor" local components, nidogens largely functioning as catalysts or molecular adaptors and perlecan as bridging stabilizer. Collectively, orchestration of BM assembly, remodeling, and the role of individual players herein are determined by the developmental, tissue-specific, or functional context.
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    ABSTRACT: Parallaxis is a programming language for massively parallel single instruction-multiple data (SIMD) systems, based on Modula-2. There are only a small number of additional constructs to handle parallel data (vectors) and data exchange among processors or between the front-end and back-end. Parallaxis helps to solve parallel problems in a natural way and does not require special skills. The major language constructs are described and a number of sample programs are given together with their simulated processor element PE-load and efficiency values. Parallaxis is available as a simulation system which is chiefly used in universities for instructional purposes. However, a compiler for the massively parallel MasPar computer system has been finished, and a compiler for the Connection Machine is being developed
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    ABSTRACT: The outer most layer of the skin, the epidermis, is attached to the dermis via a sheet of extracellular matrix proteins termed the basement membrane zone (BMZ). In the intact skin, adhesion of the keratinocytes in the basal layer of the epidermis to the BMZ is facilitated primarily by hemidesmosomes which associate with the keratin cytoskeleton. Cultured keratinocytes do not assemble bona fide hemidesmosomes although hemidesmosome protein clusters (stable anchoring contacts) are found along the substrate-attached surface of the cells and towards the leading edge of keratinocytes repopulating scratch wounds. Actin cytoskeleton-associated matrix adhesion devices termed focal contacts are not thought to play an important role in the adhesion of keratinocytes to the BMZ in intact skin but are prominent in cultured keratinocytes where they are believed to regulate cell migration. We review the molecular components, functions, dynamics and cross-talk of hemidesmosomes and focal contacts in keratinocytes. In addition, we briefly describe what is known about their role in autoimmune and genetic blistering diseases of the skin. We also discuss recent publications which indicate, contrary to expectation, that certain focal contact proteins retard keratinocyte migration while hemidesmosomal proteins regulate directed keratinocyte motility during wound healing.
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