RT Journal Article
SR Electronic
T1 Control of clathrin-mediated endocytosis by NIMA family kinases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 757427
DO 10.1101/757427
A1 Braveen B. Joseph
A1 Yu Wang
A1 Phil Edeen
A1 Vladimir Lažetić
A1 Barth D. Grant
A1 David S. Fay
YR 2019
UL http://biorxiv.org/content/early/2019/09/04/757427.abstract
AB Endocytosis, the process by which cells internalize plasma membrane and associated cargo, is regulated extensively by posttranslational modifications. Previous studies suggested the potential involvement of scores of protein kinases in endocytic control, of which only a few have been validated within their native context. Here we show that the conserved NIMA-related kinases NEKL-2/NEK8/9 and NEKL-3/NEK6/7 (the NEKLs) control clathrin-mediated endocytosis in C. elegans. Loss of NEKLs leads to clathrin mislocalization and to a dramatic reduction in clathrin mobility at the apical membrane. Strikingly, reducing the levels of active AP2, the major clathrin adapter complex, rescues nekl mutant defects, whereas increased levels of active AP2 exacerbate nekl defects. Moreover, NEKL inhibition alleviates defects associated with reduced AP2 activity, attesting to the tight link between NEKL and AP2 functions. We also show that NEKLs are required for the clustering and internalization of membrane cargo and that human NEKs rescue defects in nekl mutant worms.