Cells, Volume 11, Issue 17
2022 September-1 - 152 articles
Cover Story: MLC1-inherited mutations cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), an incurable leukodystrophy characterized by macrocephaly, chronic brain edema, cysts and myelin vacuolation. Although MLC1 genetic defects affect VRAC functionality leading to ion/water exchange defects in astrocytes, MLC1’s proper function and MLC molecular pathogenesis are still unknown. We demonstrated that MLC1 is a CaMKII target protein whose phosphorylation, occurring in response to intracellular Ca2+ release, potentiates the VRAC-mediated activation of the swelling-induced chloride currents. These findings reveal that MLC1 is a Ca2+-regulated protein, linking volume control to Ca2+ signaling in astrocytes and provide new insight for the comprehension of the defective mechanisms underlining MLC and other brain pathologies characterized by astrocyte swelling and edema. View this paper - Issues are regarded as officially published after their release is announced to the table of contents alert mailing list .
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