Proteins as receptors

Available evidence indicates that CNTs do not enter the cell directly from the plasma membrane, but are endocytosed inside the lumen of vesicular structures in a temperature- and energy-dependent process (Black and Dolly 1986 Critchley et al. 1985 Dolly et al. 1984 reviewed in Schiavo et al. 2000). The finding of SV proteins as receptors of BoNTs support the proposal (Montecucco and Schiavo 1995) that, after binding, BoNTs are endocytosed within synaptic vesicles (SV) via their retrieval to be refilled with neurotransmitter, an hypothesis originally advanced to account for the increased rate of poisoning with NMJ activity (Figure 4) (Hughes and Whaler 1962). 

The significance of cadherin-like proteins as receptors has been demonstrated by ectopic expression in different cell lines [12, 13] and is further corroborated by the presence of mutated cadherin genes in resistant Hdiothis virescens [14, 15] and Pectinophora gossypidla [16, 17] insect strains. In addition, glycolipids and glycosylated alkaline phosphatase have been implicated in Cry binding [18, 19]. 

Non-enzyme proteins as receptors. From about 1950, it began to be realized that the acetycholine receptor of muscle was a permease, namely a non-enzyme protein situated in the plasma membrane at the synapse. When coupled with ACh, it regulates the passage of sodium, potassiiun, and calcium ions (Karlin, 1974). Apparently, permeases provide the graded response needed at synapses. Initially, knowledge of permeases came from bacteria, where they were easier to isolate and study (see Section 3.1). Each molecule of ACh, by combining with its permease, allows 50 000 cations to cross the membrane (Katz and Miledi, 1972). 

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