The Anaphase
Promoting Complex/Cyclosome-Cdh1 (APC/C-Cdh1) is a multiprotein complex known
for its role in cell cycle regulation, specifically in targeting cell cycle
proteins for degradation during mitosis. However, recent studies have revealed
novel functions of APC/C-Cdh1 in postmitotic neurons. Here are some key points
regarding the functions of APC/C-Cdh1 in postmitotic neurons:
1. Neuronal Survival:
o Cyclin B1
Degradation: In postmitotic neurons, APC/C-Cdh1 promotes the continuous degradation of
cyclin B1, a key cell cycle regulator. By targeting cyclin B1 for proteasomal
degradation, APC/C-Cdh1 prevents its nuclear accumulation and inhibits cell
cycle re-entry, thereby promoting neuronal survival.
o Apoptosis
Regulation:
Dysregulation of APC/C-Cdh1-mediated cyclin B1 degradation in postmitotic
neurons can lead to aberrant cell cycle activation and apoptosis. Maintaining
proper APC/C-Cdh1 activity is crucial for preventing neuronal cell death and
ensuring long-term neuronal survival.
2. Axonal Growth and
Synaptogenesis:
o Regulation of
Developmental Processes: APC/C-Cdh1 has been implicated in regulating axonal growth and
synaptogenesis in postmitotic neurons. By controlling the degradation of
specific proteins involved in neuronal development, APC/C-Cdh1 influences the
structural and functional maturation of neurons.
o Synaptic
Connectivity: Proper functioning of APC/C-Cdh1 is essential for establishing and
maintaining synaptic connectivity in the brain. Disruption of APC/C-Cdh1
activity can impact synaptic plasticity and neuronal network formation,
potentially leading to cognitive deficits.
3. Glucidic
Metabolism:
o Metabolic
Regulation:
APC/C-Cdh1 has been linked to the regulation of glucidic (carbohydrate)
metabolism in postmitotic neurons. By modulating the stability of metabolic
enzymes or regulators, APC/C-Cdh1 may influence energy production and
utilization in neurons, thereby impacting neuronal function and viability.
o Metabolic
Homeostasis: Maintaining metabolic homeostasis is crucial for neuronal health and
function. APC/C-Cdh1-mediated control of glucidic metabolism pathways in
postmitotic neurons highlights the diverse roles of this complex beyond cell
cycle regulation.
4. In Vivo Studies:
o Mouse Models: Studies using
specific neuronal knockout mouse models for Cdh1 have demonstrated the
importance of APC/C-Cdh1 in neuronal survival in vivo. Depletion of Cdh1 in the
brain leads to selective neuronal loss, emphasizing the essential role of
APC/C-Cdh1 in maintaining neuronal integrity and function.
o Layer-Specific
Effects: Cdh1
depletion in the cerebral cortex results in a time-dependent shortening of
specific cortical layers, indicating a progressive loss of neurons. These in
vivo findings underscore the significance of APC/C-Cdh1 in preserving neuronal
populations and cortical architecture.
In conclusion,
APC/C-Cdh1 plays critical roles in postmitotic neurons beyond its canonical
function in cell cycle regulation. By influencing neuronal survival, axonal
growth, synaptogenesis, and metabolic processes, APC/C-Cdh1 contributes to the
maintenance of neuronal integrity and function. Understanding the diverse
functions of APC/C-Cdh1 in postmitotic neurons provides insights into the
molecular mechanisms underlying neuronal development, connectivity, and
metabolic homeostasis, with implications for neurodegenerative disorders and
cognitive function.
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