Programa de Oncología Translacional, Instituto de Biología
Molecular y Celular del Cáncer,
Centro de Investigación del Cáncer, CSIC-Universidad
de Salamanca, Salamanca, E-37007, Spain
Dr. P. A. Lazo, IBMCC-Centro de Investigación del Cáncer, CSIC-
Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
Tel: 34 923 294 804
Fax: 34 923 294 795
In the human proteome, there are thirty-three proteins composing
the tetraspanin (Tspan) family, which are a group of highly hydrophobic membrane
proteins defined by their structural characteristics (Figure 1). Tetraspanins
have four transmembrane domains with short intra-cytosolic N- and C-terminal
regions, and two extracellular (EC) loops (Tarrant et al., 2003). The large
EC2 loop has distinctive characteristics, such as a conserved CCG motif and
conserved cysteines permitted the identification of a protein signature (Shoham
et al., 2006), so that three tetraspanin subgroups are identified based on their
folding patterns (Seigneuret et al., 2001). The hydrophobic transmembrane regions
also contain conserved polar residues (Figure 1).
The short C-terminal region is likely to provide a link to intracellular signaling molecules (Stipp et al.,
Individual tetraspanin proteins can interact with several different
types of proteins (Levy and Shoham, 2005), most of which play a receptor role,
or alternatively couple receptors to signalling pathways. These interacting
proteins range from membrane receptors, adhesion molecules to signal transduction
molecules (Table 1).
Some of these protein-protein interactions are restricted to a specific tetraspanin
protein. The combination of tetraspanins and the proteins listed in Table 1
suggests there are multiple different combinations between tetraspanins and
their associated proteins. Although some combinations are specific, clearly
many others remain to be identified. This heterogeneity of tetraspanin interactions
with a variety of membrane proteins is likely to determine the biological role
of tetraspanins as costimulatory molecules.