Abs - Institute of Biochemistry and Biophysics

University of Tehran
Esmat Fathi
Institute of Biochemistry and Biophysics (IBB)
Seminar II- MSc
(March 9, 2014)
Reelin Glycoprotein: Structure, Biology and Roles in Health and
Disease
Brain development and function requires the coordinated genesis, migration, and maturation
of all cellular components. Reelin is a neuroprotein with crucial role during neurodevelopment
and also in postnatal period. It regulates neuronal migration and positioning in developing
neocortex and cerebellar cortex. Postnatally, it participates in regulation of dendritic and axonal
growth, synaptogenesis, neurotransmission and it contributes to synaptic plasticity necessary
for learning and memory functions. Role of Reelin seems to be rather complex and profound
studies are gradually uncovering its further functions. Deficits of Reelin were detected in
neuropsychiatric disorders such as Alzheimer's disease (AD), schizophrenia, bipolar disorder
and autism. Pathogenesis of these disorders is far from being clearly understood. Role of reelin
in these diseases seems to be vital, since its genetic variants were associated with these diseases
and often influence symptom severity. Reelin is a promising candidate molecule with potential
future applications in diagnostics and therapy, however further detailed research is essential.
For the first time, Falconer et al. discovered Reelin mutant mouse that was named
Reeler in 1951. Reelin gene (Reln) was discovered and cloned by D' Arcangelo and Curran for
the first time in 1995. Reelin is a major secretory extracellular matrix protein which has a
crucial role during in neurodevelopment and in postnatal period. This glycoprotein with 388
kDa containing 3461 residues. Reelin binding to very-low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), triggers the intracellular signaling cascade that
leads to activation of Tau protein by dephosphorylation. Finally, Reelin has a direct effect on
enhancement of long term potentiation (LTP), via direct involvement of its receptors VLDLR
and ApoER. Alternately, phorphorylation of NMDA receptor by Fyn kinase is essential for
induction of LTP and modulation of synaptic plasticity, potentially converging on Reelin’s role
in cognition and memory processing.
References:
 Alexis M. Stranahan, Joanna R. Erion, Marlena Wosiski-Kuhn (2013). Reelin signaling
in development, maintenance, and plasticity of neural networks.
 Fatemi SH (2013)."The involvement of Reelin in neurodevelopmental disorders."
Neuropharmacology 68 122-135.
 Lakatosova, S., Celec, P., Schmidtova, E., Kubranska, A (2011). The impact of
serotonergic stimulation on reelin and glutamate decarboxylase gene expression in
adult female rats. Bratisl. Lek. Listy 112, 58-62.

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