L1-Type Cell Adhesion Molecules: Distinct Roles in Synaptic Targeting, Organization, and Function

Uthaman, Smitha Babu; Godenschwege, Tanja A.

doi:10.1007/978-0-387-92708-4_12

Cited by 2 publications

(1 citation statement)

References 113 publications

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“…In vertebrates and invertebrates, the vast majority of studies involving L1-type CAM functions describe their developmental role at the plasma membrane but they are also associated with learning and memory in the adult [ 87 ] and have been recently reported to be imported to the nucleus as well [ 16 – 19 ]. Here, we show that Nrg is retrogradely transported from mature synaptic terminals in the adult.…”

Section: Discussionmentioning

confidence: 99%

Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

et al. 2017

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Here, we established the Drosophila Giant Fiber neurons (GF) as a novel model to study axonal trafficking of L1-type Cell Adhesion Molecules (CAM) Neuroglian (Nrg) in the adult CNS using live imaging. L1-type CAMs are well known for their importance in nervous system development and we previously demonstrated a role for Nrg in GF synapse formation. However, in the adult they have also been implicated in synaptic plasticity and regeneration. In addition, to its canonical role in organizing cytoskeletal elements at the plasma membrane, vertebrate L1CAM has also been shown to regulate transcription indirectly as well as directly via its import to the nucleus. Here, we intend to determine if the sole L1CAM homolog Nrg is retrogradley transported and thus has the potential to relay signals from the synapse to the soma. Live imaging of c-terminally tagged Nrg in the GF revealed that there are at least two populations of retrograde vesicles that differ in speed, and either move with consistent or varying velocity. To determine if endogenous Nrg is retrogradely transported, we inhibited two key regulators, Lissencephaly-1 (Lis1) and Dynactin, of the retrograde motor protein Dynein. Similar to previously described phenotypes for expression of poisonous subunits of Dynactin, we found that developmental knock down of Lis1 disrupted GF synaptic terminal growth and that Nrg vesicles accumulated inside the stunted terminals in both mutant backgrounds. Moreover, post mitotic Lis1 knock down in mature GFs by either RNAi or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) induced mutations, resulted in normal length terminals with fully functional GF synapses which also exhibited severe accumulation of endogenous Nrg vesicles. Thus, our data suggests that accumulation of Nrg vesicles is due to failure of retrograde transport rather than a failure of terminal development. Together with the finding that post mitotic knock down of Lis1 also disrupted retrograde transport of tagged Nrg vesicles in GF axons, it demonstrates that endogenous Nrg protein is transported from the synapse to the soma in the adult central nervous system in a Lis1-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

et al. 2017

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Neuropsin Expression Correlates with Dendritic Marker MAP2c Level in Different Brain Regions of Aging Mice

Konar

Thakur

2014

Mol Neurobiol

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Neuropsin (NP) is a serine protease, implicated in synaptic plasticity and memory acquisition through cleavage of synaptic adhesion molecule, L1CAM. However, NP has not been explored during brain aging that entails drastic deterioration of plasticity and memory with selective regional vulnerability. Therefore, we have analysed the expression of NP and correlated with its function via analysis of endogenous cleavage of L1CAM and level of dendritic marker MAP2c in different regions of the aging mouse brain. While NP expression gradually decreased in the cerebral cortex during aging, it showed a sharp rise in both olfactory bulb and hippocampus in adult and thereafter declined in old age. NP expression was moderate in young medulla, but undetectable in midbrain and cerebellum. It was positively correlated with L1CAM cleavage and MAP2c level in different brain regions during aging. Taken together, our study shows age-dependent regional variation in NP expression and its positive correlation with MAP2c level, suggesting the involvement of NP in MAP2c mediated alterations in dendritic morphology during aging.

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L1-Type Cell Adhesion Molecules: Distinct Roles in Synaptic Targeting, Organization, and Function

Cited by 2 publications

References 113 publications

Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

Neuropsin Expression Correlates with Dendritic Marker MAP2c Level in Different Brain Regions of Aging Mice

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