Axon glycoprotein routing in nerve polarity, function, and repair

• Glycan interactions regulate sorting of axonal glycoconjugates and axon function.
• Neural L1 sorting to the axon membrane depends on LacNAc termini on its N-glycans.
• The transport and function of TrkA require mature N-glycans and ganglioside GM1.
• Contactin targets myelin paranodes or nodes by modification of its N-glycans.
• A local shift of complex gangliosides to GM1 is necessary to regenerate severed axons.

Nervous system function relies on the capacity of neurons to organize specialized domains for impulse reception or transmission. Such a polarized architecture relies on highly discriminatory and efficient mechanisms for the transport and targeting of required molecules to their functional positions. Glycans play a central role in polarized traffic based on their extraordinary capacity to encrypt bio-information. Glycan-based interactions exquisitely regulate cargo selection, trafficking, and targeting to the axon membrane. This generates segregated functional domains, where basal nerve processes such as axon growth, synaptic activity, or myelination take place. Deciphering the details of the glycan structures and carbohydrate-binding molecules that underlie these mechanisms improves our knowledge of nerve physiology and defines novel specific approaches for neurological treatments.