Membrane binding, endocytic trafficking and intracellular fate of high-affinity antibodies to gangliosides GD1a and GM1

Autor: Nobuhiro Yuki, Fernando M. Ruggiero, Jose L. Daniotti, Aldo Alejandro Vilcaes
Rok vydání: 2017
Předmět:
0301 basic medicine
Endocytic cycle
Antibody Affinity
Gene Expression
Endocytic recycling
Autoantigens
Biochemistry
Mice
Gangliosides
AUTOIMMUNE NEUROPATHY
Internalization
media_common
Mice
Knockout
Neurons
ADP-Ribosylation Factors
Antibodies
Monoclonal
ANTI-GANGLIOSIDE ANTIBODY
Endocytosis
Molecular Imaging
Cell biology
INTRACELLULAR TRAFFICKING
lipids (amino acids
peptides
and proteins)
Antibody
CIENCIAS NATURALES Y EXACTAS
Intracellular
Protein Binding
Endosome
ENDOCYTOSIS
Otras Ciencias Biológicas
media_common.quotation_subject
Biophysics
CHO Cells
Endosomes
G(M1) Ganglioside
Biology
Time-Lapse Imaging
Ciencias Biológicas
03 medical and health sciences
Cricetulus
Cell Line
Tumor
Animals
Humans
Dynamin
Cell Membrane
Biological Transport
Cell Biology
GANGLIOSIDE
carbohydrates (lipids)
Kinetics
030104 developmental biology
ADP-Ribosylation Factor 6
biology.protein
Zdroj: Biochimica et Biophysica Acta (BBA) - Biomembranes. 1859:80-93
ISSN: 0005-2736
Popis: Gangliosides are glycolipids embedded in the outer leaflets of the plasma membrane. Antibodies against GM1 and GD1a gangliosides are associated with selective dysfunction of motor axons in peripheral neuropathies, and differential endocytic processing of antibodies to gangliosides represent a critical modulator of site-specific injury in Guillain-Barré syndrome. In addition, antibodies to glycolipids have emerged as an attractive tool for therapeutic interventions in cancer. In this work, we have investigated the binding, endocytosis and intracellular fate of high-affinity antibodies to gangliosides GD1a and GM1 both in epithelial and neuronal-like cells. Live cell imaging and fluorometric analysis showed that, after specific plasma membrane binding, a fraction of antibody to GD1a was slightly but rapidly internalized by a dynamin 2-independent pathway and then accumulated in the endocytic recycling compartment. We also show that internalization of antibody to GD1a is regulated by ADP-ribosylation factor 6. Surprisingly, experiment of cellular antibody uptake performed at 16 °C, widely used to accumulate the endocytic cargo in sorting endosomes, showed that the antibody to GD1a remained mostly localized at the plasma membrane, supporting the presence of selective mechanisms for cell internalization of antibody-ganglioside complex. In contrast, antibody to GM1 was endocyted in epithelial cells but remained at the plasma membrane of neuronal-like cells. Together, these results provide additional evidences about the molecular mechanisms that operate in the uptake and intracellular trafficking dynamics of antibodies to glycolipids and have significant translational implications for the understanding of clinical characteristics of anti-ganglioside antibody-mediated neuropathies and for the development of novel therapeutics targeting. Fil: Ruggiero, Fernando Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina Fil: Vilcaes, Aldo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina Fil: Yuki, Nobuhiro. Department Of Neurology, Mishima Hospital; Japón Fil: Daniotti, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Databáze: OpenAIRE
Externí odkaz: