reelin

Function

• extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex & cerebellum
• regulates microtubule function in neurons & neuronal migration
• affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration
• enzymatic activity is important for the modulation of cell adhesion
• binding to the extracellular domains of lipoprotein receptors VLDLR & apoER2 induces Tyr phosphorylation o Dab1 & modulation of Tau phosphorylation (putative)
• binds to the ectodomains of VLDLR & apoER2

Structure

• homolog of mouse protein derived from reeler gene
• the basic C-terminal region is essential for secretion
• belongs to the reelin family
• contains 16 BNR repeats
• contains 8 EGF-like domains
• contains 1 reelin domain

Compartment

• secreted, extracellular space, extracellular matrix (putative)

Alternative splicing

• named isoforms=3

Expression

• abundantly produced during brain ontogenesisby the Cajal-Retzius cells & other pioneer neurons located in the telencephalic marginal zone & by granule cells of the external granular layer of the cerebellum
• in adult brain, preferentially expressed in GABAergic interneurons of the prefrontal cortex, temporal cortex, hippocampus & glutamatergic granule cells of cerebellum
• expression is reduced to about 50% in patients with schizophrenia
• also expressed in fetal & adult liver
• expressed in fetal & postnatal brain & liver
• expression in postnatal human brain is high in the cerebellum

Pathology

• defects in RELN are the cause of lissencephaly type 2

Polymorphism

• a polymorphic GGC triplet repeat located in the 5'-UTR region of RELN gene
  • in the normal population 8-10 repeats
  • 4-23 additional repeats in autistic patients
• a rare variant in RELN (H3447R, termed COLBOS confers resilience to autosomal dominant Alzheimer's disease

More general terms

• secreted protein
• glycoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5649
• OMIM: https://mirror.omim.org/entry/257320
• OMIM: https://mirror.omim.org/entry/600514
• UniProt: http://www.uniprot.org/uniprot/P78509.html