LC3-dependent Intracellular Membrane Tubules Induced by -Protocadherins A3 and B2: A ROLE FOR INTRALUMINAL INTERACTIONS
Journal of Biological Chemistry. 2010-07-01; 285(27): 20982-20992
DOI: 10.1074/jbc.M109.092031
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Clustered protocadherins (Pcdhs) are a family of cadherin-like molecules arranged
in gene clusters (alpha, beta, and gamma). gamma-Protocadherins (Pcdh-gammas) are
involved in cell-cell interactions, but their prominent intracellular
distribution in vivo and different knock-out phenotypes suggest that these
molecules participate in still unidentified processes. We found using correlative
light and electron microscopy that Pcdh-gammaA3 and -gammaB2, but not -gammaC4,
-alpha1, or N-cadherin, generate intracellular juxtanuclear membrane tubules when
expressed in cells. These tubules recruit the autophagy marker MAP1A/1B LC3 (LC3)
but are not associated with autophagic vesicles. Lipidation of LC3 is required
for its coclustering with Pcdh-gamma tubules, suggesting the involvement of an
autophagic-like molecular cascade. Expression of wild-type LC3 with Pcdh-gammaA3
increased tubule length whereas expression of lipidation-defective LC3 decreased
tubule length relative to Pcdh-gammaA3 expressed alone. The tubules were found to
emanate from lysosomes. Deletion of the luminal/extracellular domain of
Pcdh-gammaA3 preserved lysosomal targeting but eliminated tubule formation
whereas cytoplasmic deletion eliminated both lysosomal targeting and tubule
formation. Deletion of the membrane-proximal three cadherin repeats resulted in
tubes that were narrower than those produced by full-length molecules. These
results suggest that Pcdh-gammaA and -gammaB families can influence the shape of
intracellular membranes by mediating intraluminal interactions within organelles.