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Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin

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Published on: January 17, 2012

SorCS2 binds progranulin to regulate motor neuron development.

Pernille Bogetofte Thomasen¹, Alena Salasova¹, Kasper Kjaer-Sorensen²

¹Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, and Center of Excellence PROMEMO, 8000 Aarhus C, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.

|October 28, 2023

Summary

This summary is machine-generated.

SorCS2 acts as a progranulin receptor essential for motor neuron development and nerve regeneration in zebrafish and mice. This signaling pathway influences motor neuron diversification, axon growth, and repair processes.

Keywords:

CP: Developmental biology CP: Neuroscience SorCS2 VPS10p-D receptors image segmentation light-sheet microscopy motor neurons nerve injury neurodevelopment neurotrophic signaling progranulin zebrafish

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Area of Science:

Neuroscience
Molecular Biology
Developmental Biology

Background:

Motor neuron (MN) development and nerve regeneration are complex processes involving numerous molecular interactions.
Progranulin (PGRN) is implicated in various cellular functions, but its specific role in motor neuron biology is not fully understood.

Purpose of the Study:

To identify novel receptors for progranulin (PGRN) involved in motor neuron (MN) development and nerve regeneration.
To elucidate the function of SorCS2 in MN diversification, axon outgrowth, and motor nerve regeneration.

Main Methods:

Utilized zebrafish and mouse models for genetic manipulation and functional studies.
Employed cell-fate tracing and nerve segmentation techniques to analyze MN development and innervation.
Investigated molecular interactions between SorCS2 and PGRN using biochemical assays.

Main Results:

Identified SorCS2 as a PGRN receptor crucial for MN diversification and axon outgrowth in zebrafish and mice.
SorCS2 deficiency in zebrafish led to impaired neuromuscular junction morphology and motility.
SorCS2 knockout mice exhibited altered brachial MN cell-fate decisions, innervation deficits, and delayed motor nerve regeneration.
Demonstrated that SorCS2 binds PGRN, regulating its secretion, signaling, and conversion to granulins.

Conclusions:

SorCS2 is a key progranulin receptor essential for vertebrate motor neuron development and regeneration.
PGRN-SorCS2 signaling plays a critical role in motor axon pathfinding and the maintenance of motor neuron function throughout life.
Targeting the PGRN-SorCS2 pathway may offer therapeutic strategies for neurological disorders affecting motor neurons.