Irene Nunes

TGF‐β Latency: Biological Significance and Mechanisms of Activation

Transforming growth factor (TGF‐)β is secreted as a latent complex in which the mature growth factor remains associated with its propeptide. In order to elicit a biological response, the cytokine must be released from the latent complex, a process termed latent TGF‐β activation or TGF‐β formation. Although latent TGF‐β activation is a critical step in the regulation of its activity, little is known about the molecular mechanisms that lead to the production of active TGF‐β. In this article, we present an overview of the data available on this topic, and we propose a tentative model for the mechanism of TGF‐β formation based upon the observations with different cell systems and on recent findings on the structure of the latent TGF‐β complex.

GRIFIN, a Novel Lens-specific Protein Related to the Galectin Family

The vertebrate lens is a relatively simple cellular structure that has evolved to refract light. The ability of the lens to focus light on the retina derives from a number of properties including the expression at high levels of a selection of soluble proteins referred to as the crystallins. In the present study, we have used differential cDNA display techniques to identify a novel, highly abundant and soluble lens protein. Though related to the family of soluble lectins called galectins, it does not bind β-galactoside sugars and has atypical sequences at normally conserved regions of the carbohydrate-binding domain. Like some galectin family members, it can form a stable dimer. It is expressed only in the lens and is located at the interface between lens fiber cells despite the apparent lack of any membrane-targeting motifs. This protein is designated GRIFIN (galectin-relatedinter-fiber protein) to reflect its exclusion from the galectin family given the lack of affinity for β-galactosides. Although the abundance, solubility, and lens-specific expression of GRIFIN would argue that it represents a new crystallin, its location at the fiber cell interface might suggest that its primary function is executed at the membrane.