TY - JOUR
T1 - Role of α-Dystrobrevin in the differentiation process of HL-60 cells
AU - Martínez-Vieyra, Ivette
AU - Pacheco-Tapia, Giselle
AU - Reyes-López, César
AU - Méndez-Méndez, Juan Vicente
AU - Cerecedo, Doris
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - The α-Dystrobrevin gene encodes at least five different protein isoforms, expressed in diverse tissues. The α-Dystrobrevin-1 isoform (α-Db-1) is a member of the cytoplasmic dystrophin-associated protein complex, which has a C-terminal extension comprising at least three tyrosine residues susceptible to phosphorylation in vivo. We previously described α-Db in stem-progenitor cells and blood neutrophils as playing a scaffolding role and, in association with kinesin and microtubules, α-Db promotes platelet-granule trafficking. Additionally, the microtubules must establish a balanced interaction with the lamina A/C network for appropriate nuclear morphology. Considering that the most outstanding feature during neutrophil differentiation is nuclei lobulation, we hypothesized that α-Db might possess a pivotal function during the neutrophil differentiation process. Western Blot (WB) and confocal microscope assays evidenced a differential pattern expression and a subcellular redistribution of α-Db in neutrophils derived from HL-60 cells. At the end of the differentiation process, we detected an important diminution in the expression of tubulin, kinesin, and α-Db-1. Knockdown of α-Db prevented nuclei lobulation, increased Lamin A/C and syne1 expression and augmented the roughness of derived neutrophil membrane and disturbed filopodia assembly. Our results suggest that HL-60 cells undergo extensive cytoskeletal reorganization including α-Db in order to possess lobulated nuclei when they further differentiate into neutrophils.
AB - The α-Dystrobrevin gene encodes at least five different protein isoforms, expressed in diverse tissues. The α-Dystrobrevin-1 isoform (α-Db-1) is a member of the cytoplasmic dystrophin-associated protein complex, which has a C-terminal extension comprising at least three tyrosine residues susceptible to phosphorylation in vivo. We previously described α-Db in stem-progenitor cells and blood neutrophils as playing a scaffolding role and, in association with kinesin and microtubules, α-Db promotes platelet-granule trafficking. Additionally, the microtubules must establish a balanced interaction with the lamina A/C network for appropriate nuclear morphology. Considering that the most outstanding feature during neutrophil differentiation is nuclei lobulation, we hypothesized that α-Db might possess a pivotal function during the neutrophil differentiation process. Western Blot (WB) and confocal microscope assays evidenced a differential pattern expression and a subcellular redistribution of α-Db in neutrophils derived from HL-60 cells. At the end of the differentiation process, we detected an important diminution in the expression of tubulin, kinesin, and α-Db-1. Knockdown of α-Db prevented nuclei lobulation, increased Lamin A/C and syne1 expression and augmented the roughness of derived neutrophil membrane and disturbed filopodia assembly. Our results suggest that HL-60 cells undergo extensive cytoskeletal reorganization including α-Db in order to possess lobulated nuclei when they further differentiate into neutrophils.
KW - LINC complex
KW - Lamin A/C
KW - Myeloid differentiation
KW - Promyelocytic cells
UR - http://www.scopus.com/inward/record.url?scp=85050090406&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2018.07.024
DO - 10.1016/j.yexcr.2018.07.024
M3 - Artículo
C2 - 30026031
SN - 0014-4827
VL - 370
SP - 591
EP - 600
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -