Sortilin and SorLA regulate neuronal sorting of trophic and dementia-linked proteins.
Sortilin and SorLA are members of the Vps10p domain receptor family, the Sortilins, which comprise five type I transmembrane receptors differentially expressed in neuronal tissues of the central and peripheral nervous system. Since the identification of sortilin in 1997, members of this receptor family are recognized as sorting receptors primarily in the trans-Golgi network, interacting with a wide range of ligands comprising other transmembrane receptors as well as soluble proteins from neurotrophic factors to enzymes targeted for lysosomes. Specifically, the involvement of sortilin in neutrophin signaling in healthy and injured neurons is increasingly recognized, as well as the impact of SorLA on the cellular processing of amyloid precursor protein, an important component in Alzheimer's disease. The current understanding of these issues as well as the recent recognition of a molecular link between sortilin and frontotemporal dementia is addressed in this present review.
The Lundbeck Foundation Research Centre MIND, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000 Aarhus C, Denmark. ltp@biokemi.au.dk
Lone Tjener
LT
Pallesen
Christian Bjerggaard
CB
Vaegter
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D016229:Amyloid beta-Peptides; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D000099183:Sortilin; C102582:SORL1 protein, human