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Signal Cascading
CIPA patients appear to have problems unrelated to nerves
Could Anhidrosis, poor ossification, nocioception/ thermoception, and wound healing be connected?
SCN9A is also implicated in primary erythermalgia- pain/redness in extremities,
Paroxysmal extreme pain disorder
Direct afferent nervous action
Identified in Israeli Bedouin CIPA patients by J. Cox
DMT-1 Was isolated as a factor in CIPA in a pair of Han Chinese twins
Heavy metal buildup will inhibit action potential in sensory neurons
Absence causes apoptosis
Binds to TRK family, causing phosphorylation
Role in neuroplasticity
Dylan Kritter
Populations studied include:
SCN9A- Voltage gated sodium channels
DMT-1- Divalent Metal transport channel
NGF- Neurotrophin growth factor
TRKA- NGF receptor, initiates action potential, has immunological role
FAM134B- Immunologic role, survival
of peripheral neurons
Tropomyosin Related Kinase A (Neurotrophin Receptor Tyrosine Kinase) acts as a receptor for NGF
Autophosphorylates and continues MAPK pathway, important for differentiation of neurons
Differentiates and develops
peripheral neurons
NGF activity required for expression of specific heat activated channel
Functions explain CIPA disease process very effectively
Expressed on monocytes, immunologic role
Directs innervation of neurons in postganglionic sympathetic neurons
Two novel mutations in two separate Turkish families were identified in FAM134B
FAM134B acts in cellular autophagy by sequestering ER proteins to lysosomes