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The Journal of Neuroscience, May 15, 1998, 18(10):3749-3756

A Neuronal Form of the Cell Adhesion Molecule L1 Contains a Tyrosine-Based Signal Required for Sorting to the Axonal Growth Cone

Hiroyuki Kamiguchi and Vance Lemmon

Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106

The neural cell adhesion molecule L1, which is present on axons and growth cones, plays a crucial role in the formation of major axonal tracts such as the corticospinal tract and corpus callosum. L1 is preferentially transported to axons and inserted in the growth cone membrane. However, how L1 is sorted to axons remains unclear. Tyr¹¹⁷⁶ in the L1 cytoplasmic domain is adjacent to a neuron-specific alternatively spliced sequence, RSLE (Arg-Ser-Leu-Glu). The resulting sequence of YRSLE conforms to a tyrosine-based consensus motif (YxxL) for sorting of integral membrane proteins into specific cellular compartments. To study a possible role of the YRSLE sequence in L1 sorting, chick DRG neurons were transfected with human L1 cDNA that codes for full-length L1 (L1_FL), a non-neuronal form of L1 that lacks the RSLE sequence (L1_RSLE), mutant L1 with a Y1176A substitution (L1_Y1176A), or L1 truncated immediately after the RSLE sequence (L1_C77). L1_FL and L1_C77, both of which possess the YRSLE sequence, were expressed in the axonal growth cone and to a lesser degree in the cell body. In contrast, expression of both L1_RSLE and L1_Y1176A was restricted to the cell body and proximal axonal shaft. We also found that L1_RSLE and L1_Y1176A were integrated into the plasma membrane in the cell body after missorting. These data demonstrate that the neuronal form of L1 carries the tyrosine-based sorting signal YRSLE, which is critical for sorting L1 to the axonal growth cone.

Key words: neural cell adhesion molecule; L1; axon; growth cone; protein sorting; tyrosine-based sorting signal

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18103749-08$05.00/0

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