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Mammalian galectin-1 (Gal-1), a beta-galactoside-binding lectin has a prominent role in regulating cell adhesion, cell growth and immune responses. Downregulation of these biological functions may occur via internalization of Gal-1. In the present study we have investigated the mechanism and possible mediator(s) of Gal-1 endocytosis. We show that internalization occurs at a temperature higher than 22 degrees C in an energy dependent fashion. After one hour incubation Gal-1 localizes in the Golgi system within the cells, and then disappears without accumulation in degradation compartments, such as lysosomes. Based on their strong intracellular co-localization, two glycoconjugates, GM1 ganglioside and CD7 are implicated in the sorting of internalized Gal-1 into Golgi. Other known Gal-1 binding glycoproteins on T cells (CD2, CD3, CD43 and CD45) do not cointernalize with the lectin. Internalization of Gal-1 depends on its lectin activity and follows dual pathways involving clathrin-coated vesicles and raft-dependent endocytosis.

galectin-1 (gal-1), a mammalian lectin induces apoptosis of t lymphocytes. contradictory data have resulted in confusing knowledge regarding mechanism of gal-1 induced t-cell apoptosis. in this paper we aimed to resolve this controversy by comparing cell death induced by low (1.8 µm, lowgal-1) and high (18 µm, highgal-1) concentration of soluble gal-1. we show that lowgal-1 and highgal-1 trigger phosphatidylserine exposure, generation of rafts and mitochondrial membrane depolarization. in contrast, lowgal-1 but not highgal-1 is dependent on the presence of p56 lck and Zap70 and activates caspase cascade. the results allow the conclusion that the cell-death mechanism strictly depends on the concentration of gal-1.Keywords: galectin-1 -apoptosis mechanism -concentration dependence galectin-1 (gal-1), a member of the β-galactoside binding galectin superfamily plays role in regulation of viability of activated peripheral t lymphocytes and tumor t-cell lines [7,9], hence it contributes to the immunological balance in physiological and pathological situations [16]. data describing the mechanism of gal-1 induced t-cell apoptosis have been obtained using soluble, recombinant gal-1 and remained highly controversial [1,5,7,9,10,19]. the receptor tyrosine phosphatase cd45, initially described as apoptotic receptor for gal-1 [14,15,23] has recently been shown to be dispensable [4,11,12]. Gal-1 treatment induces partial TCRζ chain phosphorylation, generating pp21ζ and limited receptor clustering at the TCR contact site [22] and hence it antagonizes with the tcr signal transduction and promotes apoptosis. accordingly we have recently described the crucial function of p56 lck and Zap70 in gal-1 induced t cell apoptosis [8,9]. our previous data [7][8][9] and those provided by other laboratories [1,10,21] support that it is a mitochondrial type of caspase-mediated cell death, however other researchers have shown that gal-1 triggers a mitochondrial route independent of the caspase cascade [5]. moreover, stowell et al. [20] have published results indicating that gal-1 prepares leukocytes for phagocytic elimination by inducing phosphatidylserine exposure on the outer surface of the plasma membrane without stimulating apoptosis.

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