The LTBPs (or latent transforming growth factor β binding proteins) are important components of the extracellular matrix (ECM) that interact with fibrillin microfibrils and have a number of different roles in microfibril biology. There are four LTBPs isoforms in the human genome (LTBP-1, -2, -3, and -4), all of which appear to associate with fibrillin and the biology of each isoform is reviewed here. The LTBPs were first identified as forming latent complexes with TGFβ by covalently binding the TGFβ propeptide (LAP) via disulfide bonds in the endoplasmic reticulum. LAP in turn is cleaved from the mature TGFβ precursor in the trans golgi network but LAP and TGFβ remain strongly bound through non-covalent interactions. LAP, TGFβ, and LTBP together form the large latent complex (LLC). LTBPs were originally thought to primarily play a role in maintaining TGFβ latency and targeting the latent growth factor to the extracellular matrix (ECM), but it has also been shown that LTBP-1 participates in TGFβ activation by integrins and may also regulate activation by proteases and other factors. LTBP-3 appears to have a role in skeletal formation including tooth development. As well as having important functions in TGFβ regulation, TGFβ-independent activities have recently been identified for LTBP-2 and LTBP-4 in stabilizing microfibril bundles and regulating elastic fiber assembly.

Corneodesmosomes, the modified desmosomes of the uppermost layers of the epidermis, play an important role in corneocyte cohesion. Corneodesmosin is a secreted glycoprotein located in the corneodesmosomal core and covalently linked to the cornified envelope of corneocytes. Its glycine-and serine-rich NH 2 -terminal domain may fold to give structural motifs similar to the glycine loops described in epidermal cytokeratins and loricrin and proposed to display adhesive properties. A chimeric protein comprising human corneodesmosin linked to the transmembrane and cytoplasmic domains of mouse E-cadherin was expressed in mouse fibroblasts to test the ability of corneodesmosin to promote cell-cell adhesion. Classic aggregation assays indicated that corneodesmosin mediates homophilic cell aggregation. Moreover, Ca 2؉ depletion showed a moderate effect on aggregation. To assess the involvement of the glycine loop domain in adhesion, full-length corneodesmosin, corneodesmosin lacking this domain, or this domain alone were expressed as glutathione S-transferase fusion proteins and tested for protein-protein interactions by overlay binding assays. The results confirmed that corneodesmosin presents homophilic interactions and indicated that its NH 2 -terminal glycine loop domain is sufficient but not strictly necessary to promote binding. Altogether, these results provide the first experimental evidence for the adhesive properties of corneodesmosin and for the involvement of its glycine loop domain in adhesion.In the course of their differentiation program, epidermal keratinocytes undergo cornification, a complex set of biochemical events associated with major morphological modifications, resulting in their transformation into corneocytes. Corneocytes, devoid of tripartite plasma membrane, are limited by a highly cross-linked insoluble protein shell, the cornified envelope (1-3). Cornification induces structural modifications of the keratinocyte desmosomes, including the disappearance of the cytoplasmic plaque that is incorporated in the cornified envelope, and the densification of the desmoglea. However, the mechanisms underlying their transformation into corneodesmosomes are still poorly understood. Corneodesmosomes mediate the strong intercellular cohesion in the cornified layers that is crucial for the physical and chemical barrier function of the epidermis. Ultimately, they are degraded at the time of desquamation (4).Human corneodesmosin (Cdsn), 1 a 52-to 56-kDa basic glycoprotein specific to the cornified epithelia and the inner root sheath of the hair follicles, is firstly detected in the secretory vesicles (i.e. keratinosomes) of the keratinocytes of the uppermost spinous layer and granular layer. It is also present in the extracellular part of the granular keratinocyte desmosomes and remains in these structures after their transformation into corneodesmosomes. In the cornified layers, Cdsn is covalently linked to the cornified envelope (5-7).Cdsn has a very high serine and glycine content (27.5 and 16%, respectively...