To better understand how pass protection synchronizes between the offensive line and running backs, we need to establish that the offensive line (from tackle to tackle) makes up five blockers to protect the quarterback. The tight end(s) and running back(s) can be a 5th, 6th, or even 7th man in protection.
How those players assigned protections know who to block will depend on defensive fronts. Normally the Center calls out the protection. He does so by identifying who each lineman will be blocking. These assignments for protections typically include assigning players to block the linebacker(s).
Linebackers that are not assigned as an offensive lineman’s responsibility are the running back’s keys to block. Because you have five offensive linemen blocking plus a running back, the offense is now running a 6-man protection.
For a base 4-3 defense (or a 4-2 with a Nickel manned up over TE):
In the common base 4-3 defense, there are 4 down linemen and 3 linebackers. Using the assignment strategy described above, the offensive line is responsible for all four of the lineman plus one of the backers. With those five defenders accounted for, the running back knows his assignment is to block the sixth defender – usually a blitzing linebacker.
Where this scenario gets muddled is if the linebacker that the running back is responsible for during pass protection does not blitz. In that case the advantage tips to the offense because the running back will quickly release into a pass route. Not only does having an extra player running a passing route give the quarterback a safety valve for an outlet pass, most running backs have a speed advantage over a linebacker, making them difficult to cover.
For a base 3-4 defense:
Odd numbered fronts (three down linemen and four linebackers) are becoming increasingly popular. A 3-4 defense is harder to complete with ideal personnel, but many defensive coordinators are drawn to the ability to disguise different looks with these groupings. Coaches have different names for different schemes, but in the interest of staying extremely basic, we’ll label the linebackers SAM, MIKE, BUCK & WILL.
Against a traditional 3-4 alignment, the Center makes a “2 mikes middle†call, which tells his fellow offensive linemen to take responsibility for the three down linemen plus the 2 backers lined up over the guards. In this scenario, the running backs would have responsibility for the 2 outside linebackers.
This is a very basic understanding how pass protection works in sync with the running backs.