TY - JOUR
T1 - Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
AU - Sobu, Yuriko
AU - Furukori, Keiko
AU - Chiba, Kyoko
AU - Nairn, Angus C.
AU - Kinjo, Masataka
AU - Hata, Saori
AU - Suzuki, Toshiharu
N1 - Funding Information:
and Technology (MEXT) in Japan, by National Institutes of Health Grant AG047270 to A.C.N., by the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development (16dm0107142h0001, 17dm0107142h0002), and by a Grant-in-Aid for Scientific Research on Innovative Areas— Platforms for Advanced Technologies and Research Resources “Advanced Bioimaging Support” to T.S.
Funding Information:
We thank George S. Bloom (University of Virginia) and Sam Gandy (Mount Sinai School of Medicine) for the kind supply of antibodies. This work was supported in part by Grants-in-Aid for JSPS Research Fellow 16J04020 to Y.S. and 15J02220 to K.C. and Grants-in-Aid for Scientific Research 15K18854 to S.H. and 262930110 and 16K14690 to T.S. from the Ministry of Education, Culture, Sports, Science
Publisher Copyright:
© 2017 Sobu et al.
PY - 2017/12
Y1 - 2017/12
N2 - Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce direct association with KLC. Replacement of these serines with Ala results in a mutant that is unable to bind kinesin-1, which impairs exit of Alcα cargo from the Golgi. Despite this deficiency, the compromised Alcα mutant was still transported, albeit improperly by vesicles following missorting of the Alcα mutant with amyloid β-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alcα in anterograde transport by providing an alternative cargo receptor for kinesin-1.
AB - Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce direct association with KLC. Replacement of these serines with Ala results in a mutant that is unable to bind kinesin-1, which impairs exit of Alcα cargo from the Golgi. Despite this deficiency, the compromised Alcα mutant was still transported, albeit improperly by vesicles following missorting of the Alcα mutant with amyloid β-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alcα in anterograde transport by providing an alternative cargo receptor for kinesin-1.
UR - http://www.scopus.com/inward/record.url?scp=85038429276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038429276&partnerID=8YFLogxK
U2 - 10.1091/mbc.E17-05-0301
DO - 10.1091/mbc.E17-05-0301
M3 - Article
C2 - 29093024
AN - SCOPUS:85038429276
SN - 1059-1524
VL - 28
SP - 3844
EP - 3856
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 26
ER -