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First published online January 10, 2007
doi: 10.1242/10.1242/jcs.03316

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BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons

Alexandre David^1,2,3,*, Marie-Catherine Tiveron^4,*, Axel Defays^1,2,3, Christophe Beclin⁴, Voahirana Camosseto^1,2,3, Evelina Gatti^1,2,3, Harold Cremer^4,, and Philippe Pierre^1,2,3,,

¹ Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France
² INSERM, U631, 13288 Marseille, France
³ CNRS, UMR6102, 13288 Marseille, France
⁴ Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR 6216, Université de la Méditerranée, Case 907, 13288 Marseille cedex 9, France

Authors for correspondence (e-mail: cremer{at}ibdm.univ-mrs.fr; pierre{at}ciml.univ-mrs.fr)

Accepted 25 October 2006

The brain-associated LAMP-like molecule (BAD-LAMP) is a new member of the family of lysosome associated membrane proteins (LAMPs). In contrast to other LAMPs, which show a widespread expression, BAD-LAMP expression in mice is confined to the postnatal brain and therein to neuronal subpopulations in layers II/III and V of the neocortex. Onset of expression strictly parallels cortical synaptogenesis. In cortical neurons, the protein is found in defined clustered vesicles, which accumulate along neurites where it localizes with phosphorylated epitopes of neurofilament H. In primary neurons, BAD-LAMP is endocytosed, but is not found in classical lysosomal/endosomal compartments. Modification of BAD-LAMP by addition of GFP revealed a cryptic lysosomal retention motif, suggesting that the cytoplasmic tail of BAD-LAMP is actively interacting with, or modified by, molecules that promote its sorting away from lysosomes. Analysis of BAD-LAMP endocytosis in transfected HeLa cells provided evidence that the protein recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. Thus, BAD-LAMP is an unconventional LAMP-like molecule and defines a new endocytic compartment in specific subtypes of cortical projection neurons. The striking correlation between the appearance of BAD-LAMP and cortical synatogenesis points towards a physiological role of this vesicular determinant for neuronal function.

Key words: Corticogenesis, Endocytosis, Synaptogenesis, LAMP, Lipid microdomains, Cortex

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