Fig. 4. Mechanism of internalization and axonal transport of NGF signaling in neurons. The NGF receptors localized on the
distal axon are activated upon binding of NGF. The ligand-receptor complex is internalized through clathrin-mediated
endocytosis (A) and is retrogradely transported to the cell body using a dynein-dependent and microtubule-dependent
transport mechanism (B). Trafficking of NGF and its receptors from the membrane surface is being started by forming
clathrin-coated vesicles (CCV) and in the next step, early sorting endosomes. p75NTR moves from early endosome to
recycling endosome and returns back to the surface. TrkA receptors are sorted from early endosomes to late endosomes
(MVB) and then are retrogradely transported on the cytoskeleton from distal axon to cell body (C). The retrograde transport
of the NGF-TrkA containing late endosomes depend on the motor protein dynein. The juxtamembrane domain of TrkA
binds to dynein light chain, and the motor domain of the dynein binds directly to the micrtotubule (B).
Arimura and Kaibuchi Nature Reviews Neuroscience 8, 194–205 (March 2007) | doi:10.1038/nrn2056
Rho GTPase effectors implicated in actin and microtubule dynamics
Govek E et al. Genes Dev. 2005;19:1-49
La crescita di un neurite è determinata dall’apposizione di nuovi
elementi citoscheletrici e di membrana
La direzione di crescita dalla polimerizzazione/depolimerizzazione
della actina del GC
Rho GTPase signaling downstream of four axon guidance cue families, the semaphorins,
ephrins, netrins, and slit proteins
Govek E et al. Genes Dev. 2005;19:1-49
©2005 by Cold Spring Harbor Laboratory Press
Neuromuscular synaptic function depends critically on the precise
spatial apposition of presynaptic motor neuron acetylcholine release
sites with high-density clusters of acetylcholine receptors (AChRs) in
the postsynaptic muscle fiber membrane. During neuromuscular
synaptogenesis, AChRs are clustered before innervation, prepatterning
a central muscle region where synapses will later be established. Motor
neuron signals refine the muscle prepattern by clustering AChRs
beneath terminals and dispersing uninnervated clusters so that AChRs
become localized to, and are stably maintained at, nascent synapses.
Over the last 15 years, work from a number of groups has uncovered
the basic signaling mechanisms that underlie these events. Musclespecific kinase (MuSK), a receptor tyrosine kinase expressed by
postsynaptic muscle fibers, is essential for the formation of aneural,
prepatterned AChR clusters as well as for the formation and
maintenance of later, innervated AChR clusters. The presynaptically
released proteoglycan agrin is now more fully understood to be
important as an anti-declustering, AChR cluster maintenance factor. A
role for the neurotransmitter ACh as a cluster dispersion factor for
noninnervated AChR clusters has also recently come to be appreciated.
Il neurone utilizza per condurre informazioni rapidamente per lunga distanze segnali elettrici Differente permeabilità della membrana alle differenti specie ioniche
EK = 61 log (K+)e/(K+)i = -105 mV
ENa = 61 log (Na+)e/(Na+)i = + 67 mV
Vm = 61 log P(K+)e + P(Na+)e + P(Cl-)i / P(K+)i + P(Na+)i + P(Cl-)e
Il neurone utilizza per condurre informazioni rapidamente per lunga distanze segnali elettrici -.
• I CANALI IONICI sono
immersi nella matrice della
membrana plasmatica. Essi
possono essere: • 1. PASSIVI: sono sempre
aperti e non influenzati dal
potenziale di membrana. Il
loro ruolo è di mantenere
stabile il potenziale di riposo
• 2. ATTIVI: si aprono solo in
risposta a determinati stimoli
(chimici o elettrici o di altra
natura fisica). Concorrono alla
generazione di potenziali che
modificano il potenziale di
riposo di una cellula,
inducendo la Difficoltà
1.  Studi strutturali
2.  Studi funzionali