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

Fernando M. Ruggiero, Aldo Alejandro Vilcaes, Nobuhiro Yuki, José L. Daniotti

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)80-93
Number of pages14
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1859
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

G(M1) Ganglioside
Antibody Affinity
Membranes
Antibodies
Gangliosides
Cell membranes
Glycolipids
Cell Membrane
Dynamin II
GD1a ganglioside
Fluorometry
Endosomes
Peripheral Nervous System Diseases
Endocytosis
Axons
Anti-Idiotypic Antibodies
Sorting
Modulators
Epithelial Cells
Recycling

Keywords

  • Anti-ganglioside antibody
  • Autoimmune neuropathy
  • Endocytosis
  • Ganglioside
  • Intracellular trafficking

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Membrane binding, endocytic trafficking and intracellular fate of high-affinity antibodies to gangliosides GD1a and GM1. / Ruggiero, Fernando M.; Vilcaes, Aldo Alejandro; Yuki, Nobuhiro; Daniotti, José L.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1859, No. 1, 01.01.2017, p. 80-93.

Research output: Contribution to journalArticle

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