A pore-forming protein drives macropinocytosis to facilitate toad water maintaining

Maintaining water balance is a real challenge for amphibians in
terrestrial environments. Our previous studies with toad Bombina maxima
discovered a pore-forming protein and trefoil factor complex βγ-CAT, which
is assembled under tight regulation depending on environmental cues. Here
we report an unexpected role for βγ-CAT in toad water maintaining.
Deletion of toad skin secretions, in which βγ-CAT is a major component,
increased animal mortality under hypertonic stress. βγ-CAT was
constitutively expressed in toad osmoregulatory organs, which was
inducible under the variation of osmotic conditions. The protein induced
and participated in macropinocytosis in vivo and in vitro. During
extracellular hyperosmosis, βγ-CAT stimulated macropinocytosis to
facilitate water import and enhanced exosomes release, which
simultaneously regulated aquaporins distribution. Collectively, these
findings uncovered that besides membrane-integrated aquaporin, a secretory
pore-forming protein can facilitate toad water maintaining via
macropinocytosis induction and exocytosis modulation, especially in
responses to osmotic stress.