Normal growth cone migration (left) goes haywire after destruction of rafts.

Neuronal growth cones have detergent-resistant membranes (DRMs), specialized cell membrane fractions enriched in GPI-anchored proteins and intracellular signaling molecules. But are the DRMs involved in regulating neurite outgrowth? Yes, say Nakai and Kamiguchi (page 1097), who developed a new technique for selectively disrupting DRMs, and used it to demonstrate the functional importance of these structures in neuronal growth cones for the first time.

The authors modified a technique called micro-scale chromophore-assisted laser inactivation (micro-CALI) to specifically disrupt the integrity of DRMs in living cells. A ligand with attached dye was bound to GM1 ganglioside in the DRMs. Upon laser irradiation, the dye produced short-lived free radicals that disrupted nearby membrane structures.

Disrupting DRMs in the peripheral domain stops growth cone migration on L1 or N-cadherin substrates, but not on a laminin substrate. The cell adhesion molecules L1 and N-cadherin apparently require DRMs for normal functioning, whereas β1 integrin, which mediates growth on laminin and is not found in DRMs, does not. Disrupting DRMs in the central domain of the growth cone instead of the peripheral domain has no effect on growth cone migration.

The findings imply that homophilic binding of L1 or N-cadherin in the peripheral domain of the growth cone generates DRM-dependent signals that direct growth cone motility and shape. The new micro-CALI technique should be useful in studying other DRM- dependent signals, and the authors also hope to determine whether the growth cone DRMs are similar or identical to lipid rafts. ▪